Sakai K

References (23)

Title : Adiponectin-Receptor Agonistic Dipeptide Tyr-Pro Stimulates the Acetylcholine Nervous System in NE-4C Cells - Cheng_2024_J.Agric.Food.Chem__
Author(s) : Cheng L , Shi C , Nakamura S , Esaki N , Ichiba Y , Tanaka M , Sakai K , Matsui T
Ref : Journal of Agricultural and Food Chemistry , : , 2024
Abstract : The dipeptide Tyr-Pro has physiological potential for intact transportability into the brain parenchyma, prevention of cognitive impairment, and an adiponectin receptor 1 (AdipoR1) agonistic effect. The present study aimed to understand the effect of Tyr-Pro on the acetylcholine (ACh) nervous system and its underlying mechanism in NE-4C nerve cells. Concentration-dependent ACh production was induced by stimulation with Tyr-Pro and AdipoRon (an AdipoR1 agonist), along with the expression of AdipoR1 and choline acetyltransferase (ChAT) in NE-4C cells. By knocking down AdipoR1 in the cells, Tyr-Pro promoted ChAT expression, along with the activations of AMPK and ERK 1/2. Tyr-Pro did not alter acetylcholinesterase or ACh receptors, indicating that the dipeptide might operate as an ACh accelerator in nerve cells. This study provides the first evidence that the AdipoR1 agonistic Tyr-Pro is a promising dipeptide responsible for the stimulation of the ACh nervous system by AdipoR1-induced ChAT activation.
ESTHER : Cheng_2024_J.Agric.Food.Chem__
PubMedSearch : Cheng_2024_J.Agric.Food.Chem__
PubMedID: 38511275

Title : Loss of ACAT1 Attenuates Atherosclerosis Aggravated by Loss of NCEH1 in Bone Marrow-Derived Cells - Yamazaki_2019_J.Atheroscler.Thromb_26_246
Author(s) : Yamazaki H , Takahashi M , Wakabayashi T , Sakai K , Yamamuro D , Takei A , Takei S , Nagashima S , Yagyu H , Sekiya M , Ebihara K , Ishibashi S
Ref : J Atheroscler Thromb , 26 :246 , 2019
Abstract : AIM: Acyl-CoA cholesterol acyltransferase 1 (ACAT1) esterifies free cholesterol to cholesteryl esters (CE), which are subsequently hydrolyzed by neutral cholesterol ester hydrolase 1 (NCEH1). The elimination of ACAT1 in vitro reduces the amounts of CE accumulated in Nceh1-deficient macrophages. The present study aimed at examining whether the loss of ACAT1 attenuates atherosclerosis which is aggravated by the loss of NCEH1 in vivo. METHODS: Low density lipoprotein receptor (Ldlr)-deficient mice were transplanted with bone marrow from wild-type mice and mice lacking ACAT1, NCEH1, or both. The four types of mice were fed a high-cholesterol diet and, then, were examined for atherosclerosis. RESULTS: The cross-sectional lesion size of the recipients of Nceh1-deficient bone marrow was 1.6-fold larger than that of the wild-type bone marrow. The lesions of the recipients of Nceh1-deficient bone marrow were enriched with MOMA2-positive macrophages compared with the lesions of the recipients of the wild-type bone marrow. The size and the macrophage content of the lesions of the recipients of bone marrow lacking both ACAT1 and NCEH1 were significantly smaller than the recipients of the Nceh1-deficient bone marrow, indicating that the loss of ACAT1 decreases the excess CE in the Nceh1-deficient lesions. The collagen-rich and/or mucin-rich areas and en face lesion size were enlarged in the recipients of the Acat1(/) bone marrow compared with those of the recipients of the WT bone marrow. CONCLUSION: The loss of ACAT1 in bone marrow-derived cells attenuates atherosclerosis, which is aggravated by the loss of NCEH1, corroborating the in vitro functions of ACAT1 (formation of CE) and NCEH1 (hydrolysis of CE).
ESTHER : Yamazaki_2019_J.Atheroscler.Thromb_26_246
PubMedSearch : Yamazaki_2019_J.Atheroscler.Thromb_26_246
PubMedID: 30282838
Gene_locus related to this paper: human-NCEH1

Title : Absence of Nceh1 augments 25-hydroxycholesterol-induced ER stress and apoptosis in macrophages - Sekiya_2014_J.Lipid.Res_55_2082
Author(s) : Sekiya M , Yamamuro D , Ohshiro T , Honda A , Takahashi M , Kumagai M , Sakai K , Nagashima S , Tomoda H , Igarashi M , Okazaki H , Yagyu H , Osuga J , Ishibashi S
Ref : J Lipid Res , 55 :2082 , 2014
Abstract : An excess of cholesterol and/or oxysterols induces apoptosis in macrophages, contributing to the development of advanced atherosclerotic lesions. In foam cells, these sterols are stored in esterified forms, which are hydrolyzed by two enzymes: neutral cholesterol ester hydrolase 1 (Nceh1) and hormone-sensitive lipase (Lipe). A deficiency in either enzyme leads to accelerated growth of atherosclerotic lesions in mice. However, it is poorly understood how the esterification and hydrolysis of sterols are linked to apoptosis. Remarkably, Nceh1-deficient thioglycollate-elicited peritoneal macrophages (TGEMs), but not Lipe-deficient TGEMs, were more susceptible to apoptosis induced by oxysterols, particularly 25-hydroxycholesterol (25-HC), and incubation with 25-HC caused massive accumulation of 25-HC ester in the endoplasmic reticulum (ER) due to its defective hydrolysis, thereby activating ER stress signaling such as induction of CCAAT/enhancer-binding protein-homologous protein (CHOP). These changes were nearly reversed by inhibition of ACAT1. In conclusion, deficiency of Nceh1 augments 25-HC-induced ER stress and subsequent apoptosis in TGEMs. In addition to reducing the cholesteryl ester content of foam cells, Nceh1 may protect against the pro-apoptotic effect of oxysterols and modulate the development of atherosclerosis.
ESTHER : Sekiya_2014_J.Lipid.Res_55_2082
PubMedSearch : Sekiya_2014_J.Lipid.Res_55_2082
PubMedID: 24891333
Gene_locus related to this paper: human-NCEH1

Title : Critical role of neutral cholesteryl ester hydrolase 1 in cholesteryl ester hydrolysis in murine macrophages - Sakai_2014_J.Lipid.Res_55_2033
Author(s) : Sakai K , Igarashi M , Yamamuro D , Ohshiro T , Nagashima S , Takahashi M , Enkhtuvshin B , Sekiya M , Okazaki H , Osuga J , Ishibashi S
Ref : J Lipid Res , 55 :2033 , 2014
Abstract : Hydrolysis of intracellular cholesteryl ester (CE) is the rate-limiting step in the efflux of cholesterol from macrophage foam cells. In mouse peritoneal macrophages (MPMs), this process is thought to involve several enzymes: hormone-sensitive lipase (Lipe), carboxylesterase 3 (Ces3), neutral CE hydrolase 1 (Nceh1). However, there is some disagreement over the relative contributions of these enzymes. To solve this problem, we first compared the abilities of several compounds to inhibit the hydrolysis of CE in cells overexpressing Lipe, Ces3, or Nceh1. Cells overexpressing Ces3 had negligible neutral CE hydrolase activity. We next examined the effects of these inhibitors on the hydrolysis of CE and subsequent cholesterol trafficking in MPMs. CE accumulation was increased by a selective inhibitor of Nceh1, paraoxon, and two nonselective inhibitors of Nceh1, (+)-AS115 and (-)-AS115, but not by two Lipe-selective inhibitors, orlistat and 76-0079. Paraoxon inhibited cholesterol efflux to apoA-I or HDL, while 76-0079 did not. These results suggest that Nceh1 plays a dominant role over Lipe in the hydrolysis of CE and subsequent cholesterol efflux in MPMs.
ESTHER : Sakai_2014_J.Lipid.Res_55_2033
PubMedSearch : Sakai_2014_J.Lipid.Res_55_2033
PubMedID: 24868095

Title : Heterologous expression system in Aspergillus oryzae for fungal biosynthetic gene clusters of secondary metabolites - Sakai_2012_Appl.Microbiol.Biotechnol_93_2011
Author(s) : Sakai K , Kinoshita H , Nihira T
Ref : Applied Microbiology & Biotechnology , 93 :2011 , 2012
Abstract : Fungal secondary metabolites have been considered promising resources in the search for novel bioactive compounds. Given the high potential of fungi as genetic resources, it is essential to find an efficient way to link biosynthetic genes to the product in a heterologous system, because many genes for the secondary metabolite in the original strain are silent under standard laboratory conditions. In a previous study, we constructed a heterologous expression system for a biosynthetic gene cluster using Aspergillus oryzae as the host. To make the host more versatile for the expression of secondary metabolism genes, the expression levels of a global regulator, laeA, were increased by placing the A. oryzae laeA gene under the control of the constitutive active pgk promoter. In the A. oryzae overexpressing laeA, two clusters of heterologous biosynthetic genes [the monacolin K (MK) gene cluster from Monascus pilosus and the terrequinone A (TQ) gene cluster from Aspergillus nidulans] were successfully overexpressed, resulting in the production of the corresponding metabolite, MK or TQ. The successful production of secondary metabolites belonging to different structural groups, namely MK as a polyketide and TQ as a hybrid of amino acid and isoprenoid, indicated that the laeA-enriched A. oryzae was a versatile host for the heterologous expression of the biosynthetic gene cluster.
ESTHER : Sakai_2012_Appl.Microbiol.Biotechnol_93_2011
PubMedSearch : Sakai_2012_Appl.Microbiol.Biotechnol_93_2011
PubMedID: 22083274
Gene_locus related to this paper: emeni-tdia

Title : Identification of mokB involved in monacolin K biosynthesis in Monascus pilosus - Sakai_2009_Biotechnol.Lett_31_1911
Author(s) : Sakai K , Kinoshita H , Nihira T
Ref : Biotechnol Lett , 31 :1911 , 2009
Abstract : Monacolin K (MK), which is widely used as an antihypercholesterolemia medicine, is produced as a fungal secondary metabolite through the polyketide pathway. The MK biosynthetic gene cluster proposed for Monascus pilosus BCRC38072 was also identified in M. pilosus NBRC4480. The mokB gene, located at the end of the putative gene cluster and possibly encoding polyketide synthase, was disrupted. The mokB disruptant did not produce MK, but accumulated an intermediate that was confirmed to be monacolin J, indicating that mokB encodes the polyketide synthase responsible for the biosynthesis of side-chain diketide moiety.
ESTHER : Sakai_2009_Biotechnol.Lett_31_1911
PubMedSearch : Sakai_2009_Biotechnol.Lett_31_1911
PubMedID: 19693441
Gene_locus related to this paper: monpi-mokd

Title : CGI-58 is an alpha\/beta-hydrolase within lipid transporting lamellar granules of differentiated keratinocytes - Akiyama_2008_Am.J.Pathol_173_1349
Author(s) : Akiyama M , Sakai K , Takayama C , Yanagi T , Yamanaka Y , McMillan JR , Shimizu H
Ref : American Journal of Pathology , 173 :1349 , 2008
Abstract : CGI-58 is the causative molecule underlying Dorfman-Chanarin syndrome, a neutral lipid storage disease exhibiting apparent clinical features of ichthyosis. CGI-58, associated with triacylglycerol hydrolysis, has an alpha/beta-hydrolase fold and is also known as the alpha/beta-hydrolase domain-containing protein 5. The purpose of this study was to elucidate the function of CGI-58 and the pathogenic mechanisms of ichthyosis in Dorfman-Chanarin syndrome. Using an anti-CGI-58 antibody, we found CGI-58 to be expressed in the upper epidermis, predominantly in the granular layer cells, as well as in neurons and hepatocytes. Immunoelectron microscopy revealed that CGI-58 was also localized to the lamellar granules (LGs), which are lipid transport and secretion granules found in keratinocytes. CGI-58 expression was markedly reduced in the epidermis of patients with harlequin ichthyosis, demonstrating defective LG formation. In cultured keratinocytes, CGI-58 expression was mildly up-regulated under high Ca(2+) conditions and markedly up-regulated in three-dimensional, organotypic cultures. In the developing human epidermis, CGI-58 immunostaining was observed at an estimated gestational age of 49 days, and CGI-58 mRNA expression was up-regulated concomitantly with both epidermal stratification and keratinocyte differentiation. CGI-58 knockdown reduced expression of keratinocyte differentiation/keratinization markers in cultured human keratinocytes. Our results indicate that CGI-58 is expressed and packaged into LGs during keratinization and likely plays crucial role(s) in keratinocyte differentiation and LG lipid metabolism, contributing to skin lipid barrier formation.
ESTHER : Akiyama_2008_Am.J.Pathol_173_1349
PubMedSearch : Akiyama_2008_Am.J.Pathol_173_1349
PubMedID: 18832586

Title : Construction of a citrinin gene cluster expression system in heterologous Aspergillus oryzae - Sakai_2008_J.Biosci.Bioeng_106_466
Author(s) : Sakai K , Kinoshita H , Shimizu T , Nihira T
Ref : J Biosci Bioeng , 106 :466 , 2008
Abstract : Filamentous fungi are considered an attractive resource for the discovery and production of bioactive compounds. To facilitate molecular breeding, biosynthetic genes must be rapidly identified. But, even after the chemical structure of a compound is identified, finding the corresponding biosynthetic genes in the fungal genome still remains a challenge. In an attempt to overcome this difficulty and to easily characterize each gene in a cluster, we constructed a heterologous expression system using Aspergillus oryzae. The approximate region covering the citrinin biosynthetic gene cluster from Monascus purpureus was introduced into A. oryzae via an Aspergillus-Escherichia coli shuttle cosmid vector without manipulating the gene structure. The transformants showed slight but reproducible citrinin production and definite transcription of the biosynthetic genes. Introducing additional copies of an activator gene (ctnA), controlled by the Aspergillus nidulans trpC promoter, into the citrinin-cluster-containing transformants enhanced the transcription of all the genes in the cluster and resulted in an almost 400-fold higher citrinin production compared to that of the parental transformant. This result suggested that CtnA controlled citrinin production in this system in the same way as in the native strain. This is the first report documenting the heterologous production of functional fungal secondary metabolites in A. oryzae following the introduction of an entire gene cluster.
ESTHER : Sakai_2008_J.Biosci.Bioeng_106_466
PubMedSearch : Sakai_2008_J.Biosci.Bioeng_106_466
PubMedID: 19111642
Gene_locus related to this paper: monpu-cita

Title : Novel duplication mutation in the patatin domain of adipose triglyceride lipase (PNPLA2) in neutral lipid storage disease with severe myopathy - Akiyama_2007_Muscle.Nerve_36_856
Author(s) : Akiyama M , Sakai K , Ogawa M , McMillan JR , Sawamura D , Shimizu H
Ref : Muscle & Nerve , 36 :856 , 2007
Abstract : Recently, mutations in PNPLA2 encoding adipose triglyceride lipase (ATGL) were reported to underlie a neutral lipid storage disease (NLSD) subgroup characterized by mild myopathy and the absence of ichthyosis. In the present study a novel homozygous PNPLA2 mutation c.475_478dupCTCC (p.Gln160ProfsX19) in the patatin domain, the ATGL active site, was detected in a woman with NLSD and severe myopathy. The present results suggest that a premature truncation mutation in the patatin domain causes NLSD with severe myopathy.
ESTHER : Akiyama_2007_Muscle.Nerve_36_856
PubMedSearch : Akiyama_2007_Muscle.Nerve_36_856
PubMedID: 17657808

Title : The genome sequence and structure of rice chromosome 1 - Sasaki_2002_Nature_420_312
Author(s) : Sasaki T , Matsumoto T , Yamamoto K , Sakata K , Baba T , Katayose Y , Wu J , Niimura Y , Cheng Z , Nagamura Y , Antonio BA , Kanamori H , Hosokawa S , Masukawa M , Arikawa K , Chiden Y , Hayashi M , Okamoto M , Ando T , Aoki H , Arita K , Hamada M , Harada C , Hijishita S , Honda M , Ichikawa Y , Idonuma A , Iijima M , Ikeda M , Ikeno M , Ito S , Ito T , Ito Y , Iwabuchi A , Kamiya K , Karasawa W , Katagiri S , Kikuta A , Kobayashi N , Kono I , Machita K , Maehara T , Mizuno H , Mizubayashi T , Mukai Y , Nagasaki H , Nakashima M , Nakama Y , Nakamichi Y , Nakamura M , Namiki N , Negishi M , Ohta I , Ono N , Saji S , Sakai K , Shibata M , Shimokawa T , Shomura A , Song J , Takazaki Y , Terasawa K , Tsuji K , Waki K , Yamagata H , Yamane H , Yoshiki S , Yoshihara R , Yukawa K , Zhong H , Iwama H , Endo T , Ito H , Hahn JH , Kim HI , Eun MY , Yano M , Jiang J , Gojobori T
Ref : Nature , 420 :312 , 2002
Abstract : The rice species Oryza sativa is considered to be a model plant because of its small genome size, extensive genetic map, relative ease of transformation and synteny with other cereal crops. Here we report the essentially complete sequence of chromosome 1, the longest chromosome in the rice genome. We summarize characteristics of the chromosome structure and the biological insight gained from the sequence. The analysis of 43.3 megabases (Mb) of non-overlapping sequence reveals 6,756 protein coding genes, of which 3,161 show homology to proteins of Arabidopsis thaliana, another model plant. About 30% (2,073) of the genes have been functionally categorized. Rice chromosome 1 is (G + C)-rich, especially in its coding regions, and is characterized by several gene families that are dispersed or arranged in tandem repeats. Comparison with a draft sequence indicates the importance of a high-quality finished sequence.
ESTHER : Sasaki_2002_Nature_420_312
PubMedSearch : Sasaki_2002_Nature_420_312
PubMedID: 12447438
Gene_locus related to this paper: orysa-Q9S7P1 , orysa-Q9FYP7 , orysa-Q5ZBH3 , orysa-Q5NA74 , orysa-Q5ZA26 , orysa-Q5JLP6 , orysa-Q94D81 , orysa-cbp , orysa-Q5VQE5 , orysa-Q8RZ95 , orysa-Q9AWW1 , orysa-Q9AS70 , orysa-Q0JK71 , orysa-Q8S1D9 , orysa-Q5N8V4 , orysa-Q943F9 , orysa-B9EWJ8 , orysa-Q5N8H1 , orysa-Q5NAI4 , orysa-Q94DP8 , orysa-Q658B2 , orysa-Q5JMQ8 , orysa-Q5QMD9 , orysa-Q5N7L1 , orysa-Q5N7J6 , orysa-Q8RYV9 , orysa-Q5SNH3 , orysa-Q94DD0 , orysa-Q8W0F0 , orysa-pir7a , orysa-pir7b , orysa-Q4VWY7 , orysa-q5jlm9 , orysa-q5na00 , orysa-q5nbu1 , orysa-Q5QLC0 , orysa-q5vnp5 , orysa-Q5VP27 , orysa-Q5ZAM8 , orysa-Q5ZBI5 , orysa-q5zc23 , orysa-Q5ZCR3 , orysa-Q8L562 , orysa-Q8L570 , orysa-Q8LQS5 , orysa-Q8RZ40 , orysa-Q8RZ79 , orysa-Q8S0U8 , orysa-Q8S0V0 , orysa-Q8S125 , orysa-Q9LHX5 , orysa-Q94E46 , orysa-Q656F2 , orysi-a2wn01 , orysi-b8a7e6 , orysi-b8a7e7 , orysj-b9eya5 , orysj-q5jl22 , orysj-q5jlw7 , orysj-q94d71

Title : Analysis of the mouse transcriptome based on functional annotation of 60,770 full-length cDNAs - Okazaki_2002_Nature_420_563
Author(s) : Okazaki Y , Furuno M , Kasukawa T , Adachi J , Bono H , Kondo S , Nikaido I , Osato N , Saito R , Suzuki H , Yamanaka I , Kiyosawa H , Yagi K , Tomaru Y , Hasegawa Y , Nogami A , Schonbach C , Gojobori T , Baldarelli R , Hill DP , Bult C , Hume DA , Quackenbush J , Schriml LM , Kanapin A , Matsuda H , Batalov S , Beisel KW , Blake JA , Bradt D , Brusic V , Chothia C , Corbani LE , Cousins S , Dalla E , Dragani TA , Fletcher CF , Forrest A , Frazer KS , Gaasterland T , Gariboldi M , Gissi C , Godzik A , Gough J , Grimmond S , Gustincich S , Hirokawa N , Jackson IJ , Jarvis ED , Kanai A , Kawaji H , Kawasawa Y , Kedzierski RM , King BL , Konagaya A , Kurochkin IV , Lee Y , Lenhard B , Lyons PA , Maglott DR , Maltais L , Marchionni L , McKenzie L , Miki H , Nagashima T , Numata K , Okido T , Pavan WJ , Pertea G , Pesole G , Petrovsky N , Pillai R , Pontius JU , Qi D , Ramachandran S , Ravasi T , Reed JC , Reed DJ , Reid J , Ring BZ , Ringwald M , Sandelin A , Schneider C , Semple CA , Setou M , Shimada K , Sultana R , Takenaka Y , Taylor MS , Teasdale RD , Tomita M , Verardo R , Wagner L , Wahlestedt C , Wang Y , Watanabe Y , Wells C , Wilming LG , Wynshaw-Boris A , Yanagisawa M , Yang I , Yang L , Yuan Z , Zavolan M , Zhu Y , Zimmer A , Carninci P , Hayatsu N , Hirozane-Kishikawa T , Konno H , Nakamura M , Sakazume N , Sato K , Shiraki T , Waki K , Kawai J , Aizawa K , Arakawa T , Fukuda S , Hara A , Hashizume W , Imotani K , Ishii Y , Itoh M , Kagawa I , Miyazaki A , Sakai K , Sasaki D , Shibata K , Shinagawa A , Yasunishi A , Yoshino M , Waterston R , Lander ES , Rogers J , Birney E , Hayashizaki Y
Ref : Nature , 420 :563 , 2002
Abstract : Only a small proportion of the mouse genome is transcribed into mature messenger RNA transcripts. There is an international collaborative effort to identify all full-length mRNA transcripts from the mouse, and to ensure that each is represented in a physical collection of clones. Here we report the manual annotation of 60,770 full-length mouse complementary DNA sequences. These are clustered into 33,409 'transcriptional units', contributing 90.1% of a newly established mouse transcriptome database. Of these transcriptional units, 4,258 are new protein-coding and 11,665 are new non-coding messages, indicating that non-coding RNA is a major component of the transcriptome. 41% of all transcriptional units showed evidence of alternative splicing. In protein-coding transcripts, 79% of splice variations altered the protein product. Whole-transcriptome analyses resulted in the identification of 2,431 sense-antisense pairs. The present work, completely supported by physical clones, provides the most comprehensive survey of a mammalian transcriptome so far, and is a valuable resource for functional genomics.
ESTHER : Okazaki_2002_Nature_420_563
PubMedSearch : Okazaki_2002_Nature_420_563
PubMedID: 12466851
Gene_locus related to this paper: mouse-1lipg , mouse-1llip , mouse-1plrp , mouse-3neur , mouse-ABH15 , mouse-abhd4 , mouse-abhd5 , mouse-Abhd8 , mouse-Abhd11 , mouse-abhda , mouse-acot4 , mouse-adcl4 , mouse-AI607300 , mouse-BAAT , mouse-bphl , mouse-C87498 , mouse-Ldah , mouse-Ces1d , mouse-Ces2e , mouse-CMBL , mouse-DGLB , mouse-dpp9 , mouse-ES10 , mouse-F135A , mouse-FASN , mouse-hslip , mouse-hyes , mouse-Kansl3 , mouse-LIPH , mouse-LIPK , mouse-lipli , mouse-LIPM , mouse-lypla1 , mouse-lypla2 , mouse-MEST , mouse-MGLL , mouse-ndr4 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-ppce , mouse-Ppgb , mouse-PPME1 , mouse-q3uuq7 , mouse-Q8BLF1 , mouse-ACOT6 , mouse-Q8C1A9 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-Q8BGG9 , mouse-Q8C167 , mouse-rbbp9 , mouse-SERHL , mouse-tssp

Title : Functional annotation of a full-length mouse cDNA collection - Kawai_2001_Nature_409_685
Author(s) : Kawai J , Shinagawa A , Shibata K , Yoshino M , Itoh M , Ishii Y , Arakawa T , Hara A , Fukunishi Y , Konno H , Adachi J , Fukuda S , Aizawa K , Izawa M , Nishi K , Kiyosawa H , Kondo S , Yamanaka I , Saito T , Okazaki Y , Gojobori T , Bono H , Kasukawa T , Saito R , Kadota K , Matsuda H , Ashburner M , Batalov S , Casavant T , Fleischmann W , Gaasterland T , Gissi C , King B , Kochiwa H , Kuehl P , Lewis S , Matsuo Y , Nikaido I , Pesole G , Quackenbush J , Schriml LM , Staubli F , Suzuki R , Tomita M , Wagner L , Washio T , Sakai K , Okido T , Furuno M , Aono H , Baldarelli R , Barsh G , Blake J , Boffelli D , Bojunga N , Carninci P , de Bonaldo MF , Brownstein MJ , Bult C , Fletcher C , Fujita M , Gariboldi M , Gustincich S , Hill D , Hofmann M , Hume DA , Kamiya M , Lee NH , Lyons P , Marchionni L , Mashima J , Mazzarelli J , Mombaerts P , Nordone P , Ring B , Ringwald M , Rodriguez I , Sakamoto N , Sasaki H , Sato K , Schonbach C , Seya T , Shibata Y , Storch KF , Suzuki H , Toyo-oka K , Wang KH , Weitz C , Whittaker C , Wilming L , Wynshaw-Boris A , Yoshida K , Hasegawa Y , Kawaji H , Kohtsuki S , Hayashizaki Y
Ref : Nature , 409 :685 , 2001
Abstract : The RIKEN Mouse Gene Encyclopaedia Project, a systematic approach to determining the full coding potential of the mouse genome, involves collection and sequencing of full-length complementary DNAs and physical mapping of the corresponding genes to the mouse genome. We organized an international functional annotation meeting (FANTOM) to annotate the first 21,076 cDNAs to be analysed in this project. Here we describe the first RIKEN clone collection, which is one of the largest described for any organism. Analysis of these cDNAs extends known gene families and identifies new ones.
ESTHER : Kawai_2001_Nature_409_685
PubMedSearch : Kawai_2001_Nature_409_685
PubMedID: 11217851
Gene_locus related to this paper: mouse-1lipg , mouse-1plip , mouse-1plrp , mouse-ABH15 , mouse-abhd5 , mouse-ABHD6 , mouse-Abhd8 , mouse-aryla , mouse-bphl , mouse-cauxin , mouse-Ces1g , mouse-CPMac , mouse-dpp8 , mouse-EPHX1 , mouse-ES10 , mouse-hslip , mouse-hyes , mouse-ABHD2 , mouse-lcat , mouse-lipli , mouse-LIPN , mouse-lypla1 , mouse-lypla2 , mouse-OVCA2 , mouse-pafa , mouse-pcp , mouse-Ppgb , mouse-PPME1 , mouse-ppt , mouse-q3uuq7 , mouse-Q9DAI6 , mouse-Q80UX8 , mouse-RISC , mouse-SERHL , mouse-SPG21 , mouse-Tex30

Title : Histaminergic descending inputs to the mesopontine tegmentum and their role in the control of cortical activation and wakefulness in the cat - Lin_1996_J.Neurosci_16_1523
Author(s) : Lin JS , Hou Y , Sakai K , Jouvet M
Ref : Journal of Neuroscience , 16 :1523 , 1996
Abstract : We have demonstrated previously the importance of histaminergic neurons in arousal mechanisms. In addition to their ascending axons, these neurons also send heavy descending inputs to the mesopontine tegmentum (MPT), which plays a key role in cortical activation during wakefulness (W). This anatomical link suggests histaminergic control of the mechanisms of the MPT relevant to behavioral states. In this study, we sought to demonstrate, at the light microscopy level, hypothalamotegmental histaminergic pathways and their topographical interaction with MPT neurons in the cat and to explore further their involvement in sleep-wake control. Using immunohistochemistry of histamine (HA), either alone or together with that of choline-acetyltransferase or tyrosine hydroxylase, a large number of very fine, short and varicose HA-positive fibers and terminal-like dots were detected in the MPT, including the laterodorsal tegmental nucleus, locus coeruleus (LC), LC alpha, and peri-LC alpha. Furthermore, these fibers and terminal-like structures were found in close proximity to a great number of cholinergic or noradrenergic neurons. We also investigated the effects of microadministration of HA agonists and antagonist into the mediodorsal pontine tegmentum on the cortical electroencephalogram (EEG) power spectra and the sleep-wake cycle in freely moving cats. Microinjection of HA or 2-thiazolylethylamine (an H1-receptor agonist) caused a long-lasting suppression of cortical slow activity and an increase in quiet wakefulness (W). Paradoxical sleep, however, was less affected. The effects of HA were attenuated by systemic or in situ pretreatment with mepyramine (an H1-receptor antagonist), which when injected alone produced an increase in slow wave sleep. Microinjection of impromidine (an H2-receptor agonist) into the same area had no effect on either the cortical EEG or W. Because MPT ascending and presumed cholinergic neurons discharge tonically during cortical activation of W and because HA causes excitation of MPT cholinergic neurons via H1 receptors, we hypothesize that the histaminergic descending afferents in the MPT would promote cortical desynchronization and W, at least partially, via activation of H1 receptors situated on cholinergic neurons and that the interactions between histaminergic and cholinergic neurons constitute an important circuit in cortical activation during W.
ESTHER : Lin_1996_J.Neurosci_16_1523
PubMedSearch : Lin_1996_J.Neurosci_16_1523
PubMedID: 8778302

Title : Responses of presumed cholinergic mesopontine tegmental neurons to carbachol microinjections in freely moving cats - el Mansari_1990_Exp.Brain.Res_83_115
Author(s) : el Mansari M , Sakai K , Jouvet M
Ref : Experimental Brain Research , 83 :115 , 1990
Abstract : The effects of microinjections of a cholinergic agonist, carbachol (0.2 microgram/0.2 microliter), were examined on three different types of rostrally projecting tonic neurons that we have reported previously in the dorsal part of the pontomesencephalic tegmentum known to contain numerous cholinergic cell bodies: 1) tonic type I slow (Type I-S); 2) tonic type I rapid (Type I-R); and 3) tonic type II (Type II) (El Mansari et al. 1989). Microinjections of carbachol near unit recording sites in freely moving cats induced within a few minutes a complete suppression of the spontaneous activity and a marked reduction in orthodromic excitation of identified and non-identified type I-S neurons. These effect lasted for approximately 90-120 min and were reversed by local (0.4 microgram/0.2 microliter) or systemic (0.1-0.2 mg/kg, i.m.) administration of atropine sulfate. In contrast, the cholinergic agonist had no consistent effects on tonic type II nor on tonic type I-R neurons. In the light of these and other recent findings, we suggested the direct inhibition of central cholinergic neurons via muscarinic receptors, on the one hand, and the cholinergic nature of type I-S, but not type I-R nor type II neurons, on the other.
ESTHER : el Mansari_1990_Exp.Brain.Res_83_115
PubMedSearch : el Mansari_1990_Exp.Brain.Res_83_115
PubMedID: 2073933

Title : Nuclei of origin of monoaminergic, peptidergic, and cholinergic afferents to the cat trigeminal motor nucleus: a double-labeling study with cholera-toxin as a retrograde tracer - Fort_1990_J.Comp.Neurol_301_262
Author(s) : Fort P , Luppi PH , Sakai K , Salvert D , Jouvet M
Ref : Journal of Comparative Neurology , 301 :262 , 1990
Abstract : The aim of the present study was to determine the brainstem afferents and the location of neurons giving rise to monoaminergic, cholinergic, and peptidergic inputs to the cat trigeminal motor nucleus (TMN). This was done in colchicine treated animals by using a very sensitive double immunostaining technique with unconjugated cholera-toxin B subunit (CT) as a retrograde tracer. After CT injections in the TMN, retrogradely labeled neurons were most frequently seen bilaterally in the nuclei reticularis parvicellularis and dorsalis of the medulla oblongata, the alaminar spinal trigeminal nucleus (magnocellular division), and the adjacent pontine juxtatrigeminal region and in the ipsilateral mesencephalic trigeminal nucleus. We further observed that inputs to the TMN arise from the medial medullary reticular formation (the nuclei retricularis magnocellularis and gigantocellularis), the principal bilateral sensory trigeminal nucleus, and the dorsolateral pontine tegmentum. In addition, the present study demonstrated that the TMN received 1) serotonergic afferents, mainly from the nuclei raphe obscurus, pallidus, and dorsalis; 2) catecholaminergic afferent projections originating exclusively in the dorsolateral pontine tegmentum, including the Kolliker-Fuse, parabrachialis lateralis, and locus subcoeruleus nuclei; further, that 3) methionin-enkephalin-like inputs were located principally in the medial medullary reticular formation (nuclei reticularis magnocellularis and gigantocellularis and nucleus paragigantocellularis lateralis), in the caudal raphe nuclei (Rpa and Rob) and the dorsolateral pontine tegmentum; 4) substance P-like immunoreactive neurons projecting to the TMN were present in the caudal raphe and Edinger-Westphal nuclei; and 5) cholinergic afferents originated in the whole extent of the nuclei reticularis parvicellularis and dorsalis including an area located ventral to the nucleus of the solitary tract at the level of the obex. In the light of these anatomical data, the present report discusses the possible physiological involvement of TMN inputs in the generation of the trigeminal jaw-closer muscular atonia occurring during the periods of paradoxical sleep in the cat.
ESTHER : Fort_1990_J.Comp.Neurol_301_262
PubMedSearch : Fort_1990_J.Comp.Neurol_301_262
PubMedID: 1702107

Title : Inhibition by carbachol microinjections of presumptive cholinergic PGO-on neurons in freely moving cats - Sakai_1990_Brain.Res_527_213
Author(s) : Sakai K , el Mansari M , Jouvet M
Ref : Brain Research , 527 :213 , 1990
Abstract : The effects of microinjections of a cholinergic agonist, carbachol (0.2 micrograms/0.2 microliters), were examined on a population of presumptive cholinergic mesopontine PGO-on neurons that presents a tonic pattern of discharge during waking and exhibits short spike bursts preceding the onset of dorsal lateral geniculate PGO waves during paradoxical sleep and slow wave sleep just prior to it. PGO-on neurons were activated antidromically by the stimulation of the dorsal lateral geniculate, pulvinar and/or medial and intralaminar thalamic nuclei. They were all characterized by a long spike duration and a slow conduction velocity. Microinjections of carbachol near unit recording sites in freely moving cats induced a complete suppression of the spontaneous tonic activity during waking, but did not suppress the spontaneous phasic burst activity during sleep. Carbachol microinjections also resulted in a marked reduction in responsiveness of PGO-on neurons to orthodromic stimulation. These spike depressant effects lasted for approximately 90-120 min and were reversed completely by a local or systemic administration of atropine sulfate. These findings point to a direct inhibition of central cholinergic PGO-on neurons via a muscarinic autoreceptor and a difference in the mechanisms underlying the generation of tonic and phasic burst activity of PGO-on neurons occurring during waking and sleep.
ESTHER : Sakai_1990_Brain.Res_527_213
PubMedSearch : Sakai_1990_Brain.Res_527_213
PubMedID: 2253034

Title : Lower brainstem afferents to the cat posterior hypothalamus: a double-labeling study - Sakai_1990_Brain.Res.Bull_24_437
Author(s) : Sakai K , Yoshimoto Y , Luppi PH , Fort P , el Mansari M , Salvert D , Jouvet M
Ref : Brain Research Bulletin , 24 :437 , 1990
Abstract : Using a double-immunostaining technique with cholera toxin (CT) as a retrograde tracer, the authors examined the cells of origin and the histochemical nature of lower brainstem afferents to the cat posterior hypothalamus. The posterior hypothalamus, in particular the lateral hypothalamic area, receives substantial afferent projections from: substantia nigra, peripeduncular nucleus, ventral tegmental area, periaqueductal grey, mesencephalic reticular formation, peribrachial region including the locus coeruleus complex, rostral raphe nuclei and the rostral part of the nucleus magnus. In addition, a moderate number of retrogradely labeled neurons was found in: Edinger-Westphal nucleus, nucleus reticularis pontis oralis, nucleus reticularis magnocellularis, caudal lateral bulbar reticular formation around the nucleus ambiguus and lateral reticular nucleus and the nucleus of the solitary tract. The posterior hypothalamus receives: 1) dopaminergic inputs from A8, A9 and A10 cell groups; 2) noradrenergic inputs from A6 and A7 pontine, as well as A1 and A2 bulbar cell groups; 3) adrenergic inputs from C1 cell group in the caudal medulla; 4) serotoninergic inputs from the rostral raphe nuclei (B6, B7 and B8 cell groups); 5) cholinergic inputs from the peribrachial region of the dorsal pontine tegmentum as well as from the nucleus reticularis magnocellularis of the medulla; 6) peptidergic inputs such as methionine-enkephalin, substance P, corticotropin-releasing factor and galanin that originate mainly in the mesencephalic periaqueductal grey, the dorsal raphe nucleus and the peribrachial region of the dorsal pontine tegmentum.
ESTHER : Sakai_1990_Brain.Res.Bull_24_437
PubMedSearch : Sakai_1990_Brain.Res.Bull_24_437
PubMedID: 1970946

Title : Unitary characteristics of presumptive cholinergic tegmental neurons during the sleep-waking cycle in freely moving cats - el Mansari_1989_Exp.Brain.Res_76_519
Author(s) : el Mansari M , Sakai K , Jouvet M
Ref : Experimental Brain Research , 76 :519 , 1989
Abstract : A total of 260 neurons were recorded in the rostral pontine tegmentum of freely moving cats during the sleep-waking cycle. Of these, 207 neurons (80%) were located in the dorsal pontine tegmentum containing monoaminergic and choline acetyltransferase (ChAT)-immunoreactive, or cholinergic neurons. In addition to presumably monoaminergic PS-off cells (n = 51) showing a cessation of discharge during paradoxical sleep (PS) and presumably cholinergic PGO-on cells (n = 40) exhibiting a burst of discharge just prior to and during ponto-geniculo-occipital (PGO) waves, we observed tonic (n = 108) and phasic (n = 61) neurons exhibiting, respectively, tonic and phasic patterns of discharge during wakefulness and/or paradoxical sleep. Of 87 tonic cells histologically localized in the dorsal pontine tegmentum rich in cholinergic neurons, 46 cells (53%) were identified as giving rise to ascending projections either to the intralaminar thalamic complex (n = 26) or to the ventrolateral posterior hypothalamus (n = 13) or to both (n = 9). Two types of tonic neurons were distinguished: 1) tonic type I neurons (n = 28), showing a tonic pattern and high rates of discharge during both waking and paradoxical sleep as compared with slow wave sleep; and 2) tonic type II neurons (n = 20), exhibiting a tonic pattern of discharge highly specific to the periods of paradoxical sleep. Tonic type I neurons were further divided into two subclasses on the basis of discharge rates during waking: a) rapid (Type I-R; n = 17); and b) slow (Type I-S; n = 11) units with a discharge frequency of more than 12 spikes/s or less than 5 spikes/s, respectively. Like monoaminergic PS-off and cholinergic PGO-on cells, both tonic type II and type I-S cells were characterized by a long spike duration (median: 3.3 and 3.5 ms), as well as by a slow conduction velocity (median = 1.8 and 1.7 m/s). In the light of these data, we discuss the possible cholinergic nature and functional significance of these ascending tonic neurons in the generation of neocortical electroencephalographic desynchronization occurring during waking and paradoxical sleep.
ESTHER : el Mansari_1989_Exp.Brain.Res_76_519
PubMedSearch : el Mansari_1989_Exp.Brain.Res_76_519
PubMedID: 2551709

Title : Monoaminergic, peptidergic, and cholinergic afferents to the cat facial nucleus as evidenced by a double immunostaining method with unconjugated cholera toxin as a retrograde tracer - Fort_1989_J.Comp.Neurol_283_285
Author(s) : Fort P , Sakai K , Luppi PH , Salvert D , Jouvet M
Ref : Journal of Comparative Neurology , 283 :285 , 1989
Abstract : Using a sensitive double immunostaining technique with unconjugated cholera-toxin B subunit as a retrograde tracer, the authors determined the nuclei of origin of monoaminergic, peptidergic, and cholinergic afferent projections to the cat facial nucleus (FN). The FN as a whole receives substantial afferent projections, with relative subnuclear differences, from the following areas: 1) the perioculomotor areas, the contralateral paralemniscal region, and the mesencephalic reticular formation dorsal to the red nucleus; 2) the ipsilateral parabrachial region and the nucleus reticularis pontis, pars ventralis; and 3) the nuclei reticularis parvicellularis, magnocellularis, ventralis, and dorsalis of the medulla. In addition, the present study demonstrated that the lateral portion of the FN receives specific projections from the contralateral medial and olivary pretectal nuclei and the ipsilateral reticular formation of the pons. It was also found that the FN receives: 1) serotoninergic inputs mainly from the nuclei raphe obscurus, pallidus, magnus, and the caudal ventrolateral bulbar reticular formation; 2) catecholaminergic afferent projections from the A7 noradrenaline cell group located in the Kolliker-Fuse, parabrachialis lateralis, and locus subcoeruleus nuclei; 3) methionin-enkephalin-like inputs originating in the pretectal complex, the nucleus paragigantocellularis lateralis and the caudal raphe nuclei; 4) substance P-like afferent projections mainly from the Edinger-Westphal complex and the caudal raphe nuclei; and 5) cholinergic afferents from an area located ventral to the nucleus of the solitary tract at the level of the obex. In the light of these anatomical data, the present report discusses the physiological significance of FN inputs relevant to tonic and phasic events occurring at the level of the facial musculature during the period of paradoxical sleep in the cat.
ESTHER : Fort_1989_J.Comp.Neurol_283_285
PubMedSearch : Fort_1989_J.Comp.Neurol_283_285
PubMedID: 2738199

Title : Mapping of cholinoceptive brainstem structures responsible for the generation of paradoxical sleep in the cat - Vanni-Mercier_1989_Arch.Ital.Biol_127_133
Author(s) : Vanni-Mercier G , Sakai K , Lin JS , Jouvet M
Ref : Archives Italiennes de Biologie , 127 :133 , 1989
Abstract : In order to determine the cholinoceptive brainstem structures critical for PS generation, we investigated the effect on PS induction of the injection of a small dose and volume (0.4 microgram/0.2 microliter) of the cholinergic agonist carbachol in the following caudal brainstem structures: 1) the caudal mesencephalic reticular formation, especially the nucleus pedunculopontinus pars compacta or X area; 2) the mediodorsal pontine tegmentum, in particular the nuclei locus coeruleus (LC), locus coeruleus alpha (LC alpha), peri-locus coeruleus alpha (peri-LC alpha) and laterodorsalis tegmenti (Ldt); 3) the pontine; and 4) bulbar gigantocellular (FTG) and magnocellular tegmental fields (FTM). We found that the only brainstem area from which a high amount of PS was induced by carbachol applications with short latencies, less than 5 minutes, is the mediodorsal pontine tegumentum, namely the LC alpha and peri-LC alpha, where ChAT-and TH- immunoreactive neurons are intermingled. Injections in an area immediately ventral to the peri-LC alpha induced physiological states resembling PS but lacking certain electrophysiological (PS-like) and behavioral components of PS (dissociated states I and II). The weak PS induction following carbachol administration in the anteromedial part of the FTG was due to the spread of the drug toward the efficient site since the latencies to PS onset were in the range of 20 to 60 minutes. No effects on PS generation were obtained after carbachol microinjections in the LC and the laterocaudal part of the FTG, while carbachol injections in the X area or in the bulbar FTG or FTM resulted in the increase of waking and the decrease of PS. In addition to these effects on PS induction, we also found that carbachol induced: 1) stereotyped PGO-like bursts when injected in the ventral part of the FTG and the rostral part of the FTM, 2) postural atonia with very short latencies, less than two minutes, when injected in the LC alpha and peri-LC alpha; and 3) hippocampal theta waves of 3-5 Hz persisting during light slow wave sleep (S1) when injected in and around the LC alpha and peri-LC alpha and in some points of the mediocaudal part of the FTG. These results support the hypothesis that PS is generated by highly localized neuronal populations and suggest that the mediodorsal pontine tegmentum (namely the nuclei LC alpha and peri-LC alpha) may represent a cholinoceptive PS generator.
ESTHER : Vanni-Mercier_1989_Arch.Ital.Biol_127_133
PubMedSearch : Vanni-Mercier_1989_Arch.Ital.Biol_127_133
PubMedID: 2774793

Title : Forebrain afferents to the cat posterior hypothalamus: a double labeling study - Yoshimoto_1989_Brain.Res.Bull_23_83
Author(s) : Yoshimoto Y , Sakai K , Luppi PH , Fort P , Salvert D , Jouvet M
Ref : Brain Research Bulletin , 23 :83 , 1989
Abstract : Using a double immunostaining technique with cholera toxin (CT) as a retrograde tracer, we examined the cells of origin and the histochemical nature of afferents to the cat posterior hypothalamus. After injection in the tuberomamillary nucleus, a number of CT-labeled cells were observed in: medial preoptic area, nuclei of the septum and the stria terminalis, amygdaloid complex, anterior hypothalamic, ventromedial hypothalamic and premamillary nuclei. CT injections in the lateral hypothalamic area gave an additional heavy labeling of neurons in: lateral preoptic area, nuclei of the diagonal band of Broca, substantia innominata, and nucleus accumbens. The posterior hypothalamus receives: 1) cholinergic inputs from the septum, the lateral preoptic area and the nuclei of the diagonal band of Broca; 2) dopaminergic afferents from A11, A13, and A14 groups; 3) histaminergic afferents from the posterior hypothalamus; and 4) peptidergic afferents such as methionin-enkephalin, galanin and neurotensin, substance P and corticotropin-releasing factor from the medial preoptic area, the nucleus of the stria terminalis and/or the posterior hypothalamic structures.
ESTHER : Yoshimoto_1989_Brain.Res.Bull_23_83
PubMedSearch : Yoshimoto_1989_Brain.Res.Bull_23_83
PubMedID: 2572308

Title : The nuclei of origin of monoaminergic, peptidergic, and cholinergic afferents to the cat nucleus reticularis magnocellularis: a double-labeling study with cholera toxin as a retrograde tracer - Luppi_1988_J.Comp.Neurol_277_1
Author(s) : Luppi PH , Sakai K , Fort P , Salvert D , Jouvet M
Ref : Journal of Comparative Neurology , 277 :1 , 1988
Abstract : Using a sensitive double-immunostaining technique with nonconjugated cholera toxin B subunit (CT) as a retrograde tracer, we examined the cells of origin and the histochemical nature of afferents to the cat nucleus reticularis magnocellularis (Mc) of the medulla oblongata. After injections of CT confined to the Mc, we found that the major afferents to the Mc arise from: (1) the lateral part of the bed nucleus of the stria terminalis, the nucleus of the anterior commissure, the preoptic area, the central nucleus of the amygdala, the posterior hypothalamus, and the nucleus of the fields of Forel; (2) the Edinger-Westphal nucleus, the mesencephalic reticular formation, and the ventrolateral part of the periaqueductal grey; (3) the nuclei locus coeruleus alpha (LC alpha), peri-LC alpha, locus subcoeruleus, and reticularis pontis oralis and caudalis; (4) the caudal raphe nuclei; and (5) the nucleus reticularis ventralis of the medulla.
ESTHER : Luppi_1988_J.Comp.Neurol_277_1
PubMedSearch : Luppi_1988_J.Comp.Neurol_277_1
PubMedID: 3198792

Title : [Localization of cholinergic neurons in the cat lower brain stem] - Sakai_1986_C.R.Acad.Sci.III_303_317
Author(s) : Sakai K , Luppi PH , Salvert D , Kimura H , Maeda T , Jouvet M
Ref : Comptes Rendus de l Academie des Sciences , 303 :317 , 1986
Abstract : The localization of cholinergic neurons in the cat lower brain stem was determined immunocytochemically with a monoclonal antibody against choline acetyltransferase (ChAT), the acetylcholine synthesizing enzyme. ChAT-positive neurons were observed in four major cell groups: cranial nerve motor and special visceromotor neurons: parasympathetic preganglionic visceromotor neurons; neurons located in the ponto-mesencephalic tegmentum including area X (or pedunculopontine tegmental nucleus), nucleus laterodorsalis tegmenti (Ldt) of Castaldi, and peri-locus coeruleus alpha (peri-alpha); and neurons located in nucleus reticularis magnocellularis (Mc) and adjacent nucleus reticularis gigantocellularis (Gc) of the medulla.
ESTHER : Sakai_1986_C.R.Acad.Sci.III_303_317
PubMedSearch : Sakai_1986_C.R.Acad.Sci.III_303_317
PubMedID: 3094850