Tu Y

References (24)

Title : A simple fluorescence detection of acetylcholinesterase with peroxidase-like catalysis from iodide - Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
Author(s) : Huang X , Cheng Y , Zhou Q , Tu Y , Yan J
Ref : Spectrochim Acta A Mol Biomol Spectrosc , 313 :124116 , 2024
Abstract : Acetylcholinesterase (AChE) is an important enzyme in the central and peripheral nervous system that regulates the balance of the neurotransmitter acetylcholine. In this work, a simple, selective and sensitive fluorescence assay was developed toward AChE activity. A conventional AChE substrate acetylthiocholine iodide (ATCI) was applied. Instead directly rendering a signaling, it was found that free iodide ions was released during the enzymatic hydrolysis of ATCI. These ions further catalyzed the oxidation of non-emissive o-phenylenediamine (OPD) into a fluorescent product. This gave a response differed from frequently-adopted sulfhydryl- -based signals and thus minimized related interferences. All materials included in this process were directly available and no additional syntheses were required. Due to the extra iodide-based catalysis included, this scheme was capable of providing a sensitive response toward AChE in the range of 0.01-8 U/L, with a limit of detection at 0.006 U/L. This method was further extended onto chlorpyrifos as an exemplary AChE inhibitor, with a detection down to 3 pM.
ESTHER : Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
PubMedSearch : Huang_2024_Spectrochim.Acta.A.Mol.Biomol.Spectrosc_313_124116
PubMedID: 38490124

Title : Intracapillary LPL levels in brown adipose tissue, visualized with an antibody-based approach, are regulated by ANGPTL4 at thermoneutral temperatures - Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2219833120
Author(s) : Song W , Yang Y , Heizer P , Tu Y , Weston TA , Kim JR , Munguia P , Jung H , Fong JL , Tran C , Ploug M , Beigneux AP , Young SG , Fong LG
Ref : Proc Natl Acad Sci U S A , 120 :e2219833120 , 2023
Abstract : Lipoprotein lipase (LPL) is secreted into the interstitial spaces by parenchymal cells and then transported into capillaries by GPIHBP1. LPL carries out the lipolytic processing of triglyceride (TG)-rich lipoproteins (TRLs), but the tissue-specific regulation of LPL is incompletely understood. Plasma levels of TG hydrolase activity after heparin injection are often used to draw inferences about intravascular LPL levels, but the validity of these inferences is unclear. Moreover, plasma TG hydrolase activity levels are not helpful for understanding LPL regulation in specific tissues. Here, we sought to elucidate LPL regulation under thermoneutral conditions (30 degreesC). To pursue this objective, we developed an antibody-based method to quantify (in a direct fashion) LPL levels inside capillaries. At 30 degreesC, intracapillary LPL levels fell sharply in brown adipose tissue (BAT) but not heart. The reduced intracapillary LPL levels were accompanied by reduced margination of TRLs along capillaries. ANGPTL4 expression in BAT increased fourfold at 30 degreesC, suggesting a potential explanation for the lower intracapillary LPL levels. Consistent with that idea, Angptl4 deficiency normalized both LPL levels and TRL margination in BAT at 30 degreesC. In Gpihbp1(-/-) mice housed at 30 degreesC, we observed an ANGPTL4-dependent decrease in LPL levels within the interstitial spaces of BAT, providing in vivo proof that ANGPTL4 regulates LPL levels before LPL transport into capillaries. In conclusion, our studies have illuminated intracapillary LPL regulation under thermoneutral conditions. Our approaches will be useful for defining the impact of genetic variation and metabolic disease on intracapillary LPL levels and TRL processing.
ESTHER : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2219833120
PubMedSearch : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2219833120
PubMedID: 36787365

Title : The lipoprotein lipase that is shuttled into capillaries by GPIHBP1 enters the glycocalyx where it mediates lipoprotein processing - Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
Author(s) : Song W , Beigneux AP , Weston TA , Chen K , Yang Y , Nguyen LP , Guagliardo P , Jung H , Tran AP , Tu Y , Tran C , Birrane G , Miyashita K , Nakajima K , Murakami M , Tontonoz P , Jiang H , Ploug M , Fong LG , Young SG
Ref : Proc Natl Acad Sci U S A , 120 :e2313825120 , 2023
Abstract : Lipoprotein lipase (LPL), the enzyme that carries out the lipolytic processing of triglyceride-rich lipoproteins (TRLs), is synthesized by adipocytes and myocytes and secreted into the interstitial spaces. The LPL is then bound by GPIHBP1, a GPI-anchored protein of endothelial cells (ECs), and transported across ECs to the capillary lumen. The assumption has been that the LPL that is moved into capillaries remains attached to GPIHBP1 and that GPIHBP1 serves as a platform for TRL processing. In the current studies, we examined the validity of that assumption. We found that an LPL-specific monoclonal antibody (mAb), 88B8, which lacks the ability to detect GPIHBP1-bound LPL, binds avidly to LPL within capillaries. We further demonstrated, by confocal microscopy, immunogold electron microscopy, and nanoscale secondary ion mass spectrometry analyses, that the LPL detected by mAb 88B8 is located within the EC glycocalyx, distant from the GPIHBP1 on the EC plasma membrane. The LPL within the glycocalyx mediates the margination of TRLs along capillaries and is active in TRL processing, resulting in the delivery of lipoprotein-derived lipids to immediately adjacent parenchymal cells. Thus, the LPL that GPIHBP1 transports into capillaries can detach and move into the EC glycocalyx, where it functions in the intravascular processing of TRLs.
ESTHER : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
PubMedSearch : Song_2023_Proc.Natl.Acad.Sci.U.S.A_120_e2313825120
PubMedID: 37871217

Title : Electrostatic sheathing of lipoprotein lipase is essential for its movement across capillary endothelial cells - Song_2022_J.Clin.Invest_132_
Author(s) : Song W , Beigneux AP , Winther AL , Kristensen KK , Gronnemose AL , Yang Y , Tu Y , Munguia P , Morales J , Jung H , de Jong PJ , Jung CJ , Miyashita K , Kimura T , Nakajima K , Murakami M , Birrane G , Jiang H , Tontonoz P , Ploug M , Fong LG , Young SG
Ref : J Clinical Investigation , 132 : , 2022
Abstract : GPIHBP1, an endothelial cell (EC) protein, captures lipoprotein lipase (LPL) within the interstitial spaces (where it is secreted by myocytes and adipocytes) and transports it across ECs to its site of action in the capillary lumen. GPIHBP1's 3-fingered LU domain is required for LPL binding, but the function of its acidic domain (AD) has remained unclear. We created mutant mice lacking the AD and found severe hypertriglyceridemia. As expected, the mutant GPIHBP1 retained the capacity to bind LPL. Unexpectedly, however, most of the GPIHBP1 and LPL in the mutant mice was located on the abluminal surface of ECs (explaining the hypertriglyceridemia). The GPIHBP1-bound LPL was trapped on the abluminal surface of ECs by electrostatic interactions between the large basic patch on the surface of LPL and negatively charged heparan sulfate proteoglycans (HSPGs) on the surface of ECs. GPIHBP1 trafficking across ECs in the mutant mice was normalized by disrupting LPL-HSPG electrostatic interactions with either heparin or an AD peptide. Thus, GPIHBP1's AD plays a crucial function in plasma triglyceride metabolism; it sheathes LPL's basic patch on the abluminal surface of ECs, thereby preventing LPL-HSPG interactions and freeing GPIHBP1-LPL complexes to move across ECs to the capillary lumen.
ESTHER : Song_2022_J.Clin.Invest_132_
PubMedSearch : Song_2022_J.Clin.Invest_132_
PubMedID: 35229724

Title : Biological evaluation, molecular modeling and dynamics simulation of phenanthrenes isolated from Bletilla striata as butyrylcholinesterase inhibitors - Liu_2022_Sci.Rep_12_13649
Author(s) : Liu Y , Tu Y , Kang Y , Zhu C , Wu C , Chen G , Liu Z , Li Y
Ref : Sci Rep , 12 :13649 , 2022
Abstract : As part of our continuous studies on natural cholinesterase inhibitors from plant kingdom, the 95% ethanol extract from tubers of Bletilla striata showed promising butyrylcholinesterase (BChE) inhibition (IC(50) = 8.6 microg/mL). The extracts with different polarities (petroleum ether, ethyl acetate, n-butanol, and water) were prepared and evaluated for their inhibition of cholinesterases. The most active ethyl acetate extract was subjected to a bioassay-guided isolation and afforded twenty-two bibenzyls and phenanthrenes (1-22). All isolates were further evaluated for their BChE inhibition activity, and five phenanthrenes presented promising capacity (IC(50) < 10 microM). Further kinetic studies indicated their modes of inhibition. Compounds 6, 8, and 14 were found to be mixed-type inhibitors, while compounds 10 and 12 could be classified as non-competitive inhibitors. The potential interaction mechanism of them with BChE was demonstrated by molecular docking and molecular dynamics simulation, showing that they could interact with catalytic active site and peripheral anionic site of BChE. These natural phenanthrenes provide new scaffold for the further design and optimization, with the aim to discover new selective BChE inhibitors for the treatment of AD.
ESTHER : Liu_2022_Sci.Rep_12_13649
PubMedSearch : Liu_2022_Sci.Rep_12_13649
PubMedID: 35953511

Title : The relationship between pesticide exposure during critical neurodevelopment and autism spectrum disorder: A narrative review - He_2021_Environ.Res_203_111902
Author(s) : He X , Tu Y , Song Y , Yang G , You M
Ref : Environ Research , 203 :111902 , 2021
Abstract : Agricultural pesticides have been one of the most extensively used compounds throughout the world. The main sources of contamination for humans are dietary intake and occupational exposure. The impairments caused by agricultural pesticide exposure have been a significant global public health problem. Recent studies have shown that low-level agricultural pesticide exposure during the critical period of neurodevelopment (pregnancy and lactation) is closely related to autism spectrum disorder (ASD). Inhibition of acetylcholinesterase, gut microbiota, neural dendrite morphology, synaptic function, and glial cells are targets for the effects of pesticides during nervous system development. In the present review, we summarize the associations between several highly used and frequently studied pesticides (e.g., glyphosate, chlorpyrifos, pyrethroids, and avermectins) and ASD. We also discusse future epidemiological and toxicological research directions on the relationship between pesticides and ASD.
ESTHER : He_2021_Environ.Res_203_111902
PubMedSearch : He_2021_Environ.Res_203_111902
PubMedID: 34416252

Title : The structural basis for monoclonal antibody 5D2 binding to the tryptophan-rich loop of lipoprotein lipase - Luz_2020_J.Lipid.Res_61_1347
Author(s) : Luz JG , Beigneux AP , Asamoto DK , He C , Song W , Allan CM , Morales J , Tu Y , Kwok A , Cottle T , Meiyappan M , Fong LG , Kim JE , Ploug M , Young SG , Birrane G
Ref : J Lipid Res , 61 :1347 , 2020
Abstract : For three decades, the LPL-specific monoclonal antibody 5D2 has been used to investigate LPL structure/function and intravascular lipolysis. 5D2 has been used to measure LPL levels, block the triglyceride hydrolase activity of LPL, and prevent the propensity of concentrated LPL preparations to form homodimers. Two early studies on the location of the 5D2 epitope reached conflicting conclusions, but the more convincing report suggested that 5D2 binds to a tryptophan (Trp)-rich loop in the carboxyl terminus of LPL. The same loop had been implicated in lipoprotein binding. Using surface plasmon resonance, we showed that 5D2 binds with high affinity to a synthetic LPL peptide containing the Trp-rich loop of human (but not mouse) LPL. We also showed, by both fluorescence and UV resonance Raman spectroscopy, that the Trp-rich loop binds lipids. Finally, we used X-ray crystallography to solve the structure of the Trp-rich peptide bound to a 5D2 Fab fragment. The Trp-rich peptide contains a short alpha-helix, with two Trps projecting into the antigen recognition site. A proline substitution in the alpha-helix, found in mouse LPL, is expected to interfere with several hydrogen bonds, explaining why 5D2 cannot bind to mouse LPL.
ESTHER : Luz_2020_J.Lipid.Res_61_1347
PubMedSearch : Luz_2020_J.Lipid.Res_61_1347
PubMedID: 32690595

Title : An upstream enhancer regulates Gpihbp1 expression in a tissue-specific manner - Allan_2019_J.Lipid.Res_60_869
Author(s) : Allan CM , Heizer PJ , Tu Y , Sandoval NP , Jung RS , Morales JE , Sajti E , Troutman TD , Saunders TL , Cusanovich DA , Beigneux AP , Romanoski CE , Fong LG , Young SG
Ref : J Lipid Res , 60 :869 , 2019
Abstract : Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), the protein that shuttles LPL to the capillary lumen, is essential for plasma triglyceride metabolism. When GPIHBP1 is absent, LPL remains stranded within the interstitial spaces and plasma triglyceride hydrolysis is impaired, resulting in severe hypertriglyceridemia. While the functions of GPIHBP1 in intravascular lipolysis are reasonably well understood, no one has yet identified DNA sequences regulating GPIHBP1 expression. In the current studies, we identified an enhancer element located approximately 3.6 kb upstream from exon 1 of mouse Gpihbp1. To examine the importance of the enhancer, we used CRISPR/Cas9 genome editing to create mice lacking the enhancer (Gpihbp1 (Enh/Enh)). Removing the enhancer reduced Gpihbp1 expression by >90% in the liver and by approximately 50% in heart and brown adipose tissue. The reduced expression of GPIHBP1 was insufficient to prevent LPL from reaching the capillary lumen, and it did not lead to hypertriglyceridemia-even when mice were fed a high-fat diet. Compound heterozygotes (Gpihbp1 (Enh/-) mice) displayed further reductions in Gpihbp1 expression and exhibited partial mislocalization of LPL (increased amounts of LPL within the interstitial spaces of the heart), but the plasma triglyceride levels were not perturbed. The enhancer element that we identified represents the first insight into DNA sequences controlling Gpihbp1 expression.
ESTHER : Allan_2019_J.Lipid.Res_60_869
PubMedSearch : Allan_2019_J.Lipid.Res_60_869
PubMedID: 30598475

Title : GPIHBP1 expression in gliomas promotes utilization of lipoprotein-derived nutrients - Hu_2019_Elife_8_e47178
Author(s) : Hu X , Matsumoto K , Jung RS , Weston TA , Heizer PJ , He C , Sandoval NP , Allan CM , Tu Y , Vinters HV , Liau LM , Ellison RM , Morales JE , Baufeld LJ , Bayley NA , He L , Betsholtz C , Beigneux AP , Nathanson DA , Gerhardt H , Young SG , Fong LG , Jiang H
Ref : Elife , 8 : , 2019
Abstract : GPIHBP1, a GPI-anchored protein of capillary endothelial cells, binds lipoprotein lipase (LPL) within the subendothelial spaces and shuttles it to the capillary lumen. GPIHBP1-bound LPL is essential for the margination of triglyceride-rich lipoproteins (TRLs) along capillaries, allowing the lipolytic processing of TRLs to proceed. In peripheral tissues, the intravascular processing of TRLs by the GPIHBP1-LPL complex is crucial for the generation of lipid nutrients for adjacent parenchymal cells. GPIHBP1 is absent from the capillaries of the brain, which uses glucose for fuel; however, GPIHBP1 is expressed in the capillaries of mouse and human gliomas. Importantly, the GPIHBP1 in glioma capillaries captures locally produced LPL. We use NanoSIMS imaging to show that TRLs marginate along glioma capillaries and that there is uptake of TRL-derived lipid nutrients by surrounding glioma cells. Thus, GPIHBP1 expression in gliomas facilitates TRL processing and provides a source of lipid nutrients for glioma cells.
ESTHER : Hu_2019_Elife_8_e47178
PubMedSearch : Hu_2019_Elife_8_e47178
PubMedID: 31169500

Title : Bioactivity-guided identification of flavonoids with cholinesterase and beta-amyloid peptide aggregation inhibitory effects from the seeds of Millettia pachycarpa - Tu_2019_Bioorg.Med.Chem.Lett_29_1194
Author(s) : Tu Y , Wu C , Kang Y , Li Q , Zhu C , Li Y
Ref : Bioorganic & Medicinal Chemistry Lett , 29 :1194 , 2019
Abstract : Millettia pachycarpa Benth, a widely used anthelminthic drug in folk, is rich in flavonoids with various bioactivities. This study aimed to identify active flavonoids with anti-Alzheimer's disease (AD) effect from its seeds by a bioassay-guided isolation. A novel rotenoid with unusual oxidative ring-opening skeleton (10) and nine known flavonoids (1-9) were obtained, and their structures were elucidated by NMR and HR-ESIMS analysis. Among all isolates, 7 and 8 showed selective butyrylcholinesterase (BChE) inhibitory activities (IC50=2.34 and 11.49muM, respectively), while 3 was classified as a dual-action inhibitor against acetylcholinesterase (AChE) and BChE (IC50 AChE=17.14muM, IC50 BChE=5.68muM). Further kinetic study revealed that 3, 7, and 8 were mixed-type BChE inhibitors, but 3 was a competitive AChE inhibitor. Their strong binding affinities to BChE were confirmed by fluorescence quenching analysis. Additionally, 3 and 8 exhibited potent inhibitory effects against beta-amyloid peptide aggregation. These results revealed M. pachycarpa could be a valuable source for anti-AD leads development, and compounds 3, 7 and 8 were worthy of further study as multifunctional or specific agents for AD treatment.
ESTHER : Tu_2019_Bioorg.Med.Chem.Lett_29_1194
PubMedSearch : Tu_2019_Bioorg.Med.Chem.Lett_29_1194
PubMedID: 30910460

Title : Impaired thermogenesis and sharp increases in plasma triglyceride levels in GPIHBP1-deficient mice during cold exposure - Larsson_2018_J.Lipid.Res_59_706
Author(s) : Larsson M , Allan CM , Heizer PJ , Tu Y , Sandoval NP , Jung RS , Walzem RL , Beigneux AP , Young SG , Fong LG
Ref : J Lipid Res , 59 :706 , 2018
Abstract : Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), an endothelial cell protein, binds LPL in the subendothelial spaces and transports it to the capillary lumen. In Gpihbp1(-/-) mice, LPL remains stranded in the subendothelial spaces, causing hypertriglyceridemia, but how Gpihbp1(-/-) mice respond to metabolic stress (e.g., cold exposure) has never been studied. In wild-type mice, cold exposure increases LPL-mediated processing of triglyceride-rich lipoproteins (TRLs) in brown adipose tissue (BAT), providing fuel for thermogenesis and leading to lower plasma triglyceride levels. We suspected that defective TRL processing in Gpihbp1(-/-) mice might impair thermogenesis and blunt the fall in plasma triglyceride levels. Indeed, Gpihbp1(-/-) mice exhibited cold intolerance, but the effects on plasma triglyceride levels were paradoxical. Rather than falling, the plasma triglyceride levels increased sharply (from approximately 4,000 to approximately 15,000 mg/dl), likely because fatty acid release by peripheral tissues drives hepatic production of TRLs that cannot be processed. We predicted that the sharp increase in plasma triglyceride levels would not occur in Gpihbp1(-/-)Angptl4(-/-) mice, where LPL activity is higher and baseline plasma triglyceride levels are lower. Indeed, the plasma triglyceride levels in Gpihbp1(-/-)Angptl4(-/-) mice fell during cold exposure. Metabolic studies revealed increased levels of TRL processing in the BAT of Gpihbp1(-/-)Angptl4(-/-) mice.
ESTHER : Larsson_2018_J.Lipid.Res_59_706
PubMedSearch : Larsson_2018_J.Lipid.Res_59_706
PubMedID: 29449313

Title : Discovery of novel rivastigmine-hydroxycinnamic acid hybrids as multi-targeted agents for Alzheimer's disease - Chen_2017_Eur.J.Med.Chem_125_784
Author(s) : Chen Z , Digiacomo M , Tu Y , Gu Q , Wang S , Yang X , Chu J , Chen Q , Han Y , Chen J , Nesi G , Sestito S , Macchia M , Rapposelli S , Pi R
Ref : Eur Journal of Medicinal Chemistry , 125 :784 , 2017
Abstract : A series of rivastigmine-caffeic acid and rivastigmine-ferulic acid hybrids were designed, synthesized, and evaluated as multifunctional agents for Alzheimer's disease (AD) in vitro. The new compounds exerted antioxidant neuroprotective properties and good cholinesterases (ChE) inhibitory activities. Some of them also inhibited amyloid protein (Abeta) aggregation. In particular, compound 5 emerged as promising drug candidates endowed with neuroprotective potential, ChE inhibitory, Abeta self-aggregation inhibitory and copper chelation properties. These data suggest that compound 5 offers an attractive starting point for further lead optimization in the drug-discovery process against AD.
ESTHER : Chen_2017_Eur.J.Med.Chem_125_784
PubMedSearch : Chen_2017_Eur.J.Med.Chem_125_784
PubMedID: 27736684

Title : Forebrain-selective AMPA-receptor antagonism guided by TARP gamma-8 as an antiepileptic mechanism - Kato_2016_Nat.Med_22_1496
Author(s) : Kato AS , Burris KD , Gardinier KM , Gernert DL , Porter WJ , Reel J , Ding C , Tu Y , Schober DA , Lee MR , Heinz BA , Fitch TE , Gleason SD , Catlow JT , Yu H , Fitzjohn SM , Pasqui F , Wang H , Qian Y , Sher E , Zwart R , Wafford KA , Rasmussen K , Ornstein PL , Isaac JT , Nisenbaum ES , Bredt DS , Witkin JM
Ref : Nat Med , 22 :1496 , 2016
Abstract : Pharmacological manipulation of specific neural circuits to optimize therapeutic index is an unrealized goal in neurology and psychiatry. AMPA receptors are important for excitatory synaptic transmission, and their antagonists are antiepileptic. Although efficacious, AMPA-receptor antagonists, including perampanel (Fycompa), the only approved antagonist for epilepsy, induce dizziness and motor impairment. We hypothesized that blockade of forebrain AMPA receptors without blocking cerebellar AMPA receptors would be antiepileptic and devoid of motor impairment. Taking advantage of an AMPA receptor auxiliary protein, TARP gamma-8, which is selectively expressed in the forebrain and modulates the pharmacological properties of AMPA receptors, we discovered that LY3130481 selectively antagonized recombinant and native AMPA receptors containing gamma-8, but not gamma-2 (cerebellum) or other TARP members. Two amino acid residues unique to gamma-8 determined this selectivity. We also observed antagonism of AMPA receptors expressed in hippocampal, but not cerebellar, tissue from an patient with epilepsy. Corresponding to this selective activity, LY3130481 prevented multiple seizure types in rats and mice and without motor side effects. These findings demonstrate the first rationally discovered molecule targeting specific neural circuitries for therapeutic advantage.
ESTHER : Kato_2016_Nat.Med_22_1496
PubMedSearch : Kato_2016_Nat.Med_22_1496
PubMedID: 27820603

Title : A New Flavonoid Glycoside from Lysionotus pauciflorus - Luo_2016_Nat.Prod.Commun_11_621
Author(s) : Luo W , Wen Y , Tu Y , Du H , Li Q , Zhu C , Li Y
Ref : Nat Prod Commun , 11 :621 , 2016
Abstract : Ten flavonoids (1-10), including a new glycoside (nevadensin-7-sambubioside, 7), together with a phenylpropanoid glycoside (11) were isolated from Lysionotus pauciflorus. Their structures were elucidated by a combination of spectroscopic methods and comparing with literature data. Five compounds (1, 3, 4, 8, and 9) were obtained from the family Gesneriaceae for the first time. The new compound was evaluated in vitro for anticholinesterase activities against acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), but was found to be inactive.
ESTHER : Luo_2016_Nat.Prod.Commun_11_621
PubMedSearch : Luo_2016_Nat.Prod.Commun_11_621
PubMedID: 27319133

Title : Anticholinesterases and antioxidant alkamides from Piper nigrum fruits - Tu_2015_Nat.Prod.Res__1
Author(s) : Tu Y , Zhong Y , Du H , Luo W , Wen Y , Li Q , Zhu C , Li Y
Ref : Nat Prod Res , :1 , 2015
Abstract : The anticholinesterase and antioxidant effects of five different extracts of Piper nigrum were evaluated. Twenty-one known alkamides were isolated from active ethyl acetate extract and investigated for their cholinesterase inhibitory and antioxidant effects. Among them, piperine (2), piperettine (5) and piperettyline (20) exhibited dual inhibition against AChE and BChE, and feruperine (18) was the most potent selective inhibitor of BChE. Molecular docking simulation was performed to get insight into the binding interactions of the ligands and enzymes. In addition, N-trans-feruloyltyramine (3) contributed to the strongest DPPH radical-scavenging activity. The self-induced Abeta aggregation inhibition of 2, 5 and 18 was further evaluated. Results indicated that some alkamides could be multifunctional lead candidates for Alzheimer's disease therapy.
ESTHER : Tu_2015_Nat.Prod.Res__1
PubMedSearch : Tu_2015_Nat.Prod.Res__1
PubMedID: 26407107

Title : Lactoferrin-modified PEG-co-PCL nanoparticles for enhanced brain delivery of NAP peptide following intranasal administration - Liu_2013_Biomaterials_34_3870
Author(s) : Liu Z , Jiang M , Kang T , Miao D , Gu G , Song Q , Yao L , Hu Q , Tu Y , Pang Z , Chen H , Jiang X , Gao X , Chen J
Ref : Biomaterials , 34 :3870 , 2013
Abstract : Development of effective non-invasive drug delivery systems is of great importance to the treatment of Alzheimer's diseases and has made great progress in recent years. In this work, lactoferrin (Lf), a natural iron binding protein, whose receptor is highly expressed in both respiratory epithelial cells and neurons is here utilized to facilitate the nose-to-brain drug delivery of neuroprotection peptides. The Lf-conjugated PEG-PCL nanoparticle (Lf-NP) was constructed via a maleimide-thiol reaction with the Lf conjugation confirmed by CBQCA Protein Quantitation and XPS analysis. Other important parameters such as particle size distribution, zeta potential and in vitro release of fluorescent probes were also characterized. Compared with unmodified nanoparticles (NP), Lf-NP exhibited a significantly enhanced cellular accumulation in 16HBE14o-cells through both caveolae-/clathrin-mediated endocytosis and direct translocation. Following intranasal administration, Lf-NP facilitated the brain distribution of the coumarin-6 incorporated with the AUC0-8h in rat cerebrum (with hippocampus removed), cerebellum, olfactory tract, olfactory bulb and hippocampus 1.36, 1.53, 1.70, 1.57 and 1.23 times higher than that of coumarin-6 carried by NP, respectively. Using a neuroprotective peptide - NAPVSIPQ (NAP) as the model drug, the neuroprotective and memory improvement effect of Lf-NP was observed even at lower dose than that of NP in a Morris water maze experiment, which was also confirmed by the evaluation of acetylcholinesterase, choline acetyltransferase activity and neuronal degeneration in the mice hippocampus. In conclusion, Lf-NP may serve as a promising nose-to-brain drug delivery carrier especially for peptides and proteins.
ESTHER : Liu_2013_Biomaterials_34_3870
PubMedSearch : Liu_2013_Biomaterials_34_3870
PubMedID: 23453061

Title : Reciprocal metabolic perturbations in the adipose tissue and liver of GPIHBP1-deficient mice - Weinstein_2012_Arterioscler.Thromb.Vasc.Biol_32_230
Author(s) : Weinstein MM , Goulbourne CN , Davies BS , Tu Y , Barnes RH, 2nd , Watkins SM , Davis R , Reue K , Tontonoz P , Beigneux AP , Fong LG , Young SG
Ref : Arterioscler Thromb Vasc Biol , 32 :230 , 2012
Abstract : OBJECTIVE: Gpihbp1-deficient (Gpihbp1-/-) mice lack the ability to transport lipoprotein lipase to the capillary lumen, resulting in mislocalization of lipoprotein lipase within tissues, defective lipolysis of triglyceride-rich lipoproteins, and chylomicronemia. We asked whether GPIHBP1 deficiency and mislocalization of catalytically active lipoprotein lipase would alter the composition of triglycerides in adipose tissue or perturb the expression of lipid biosynthetic genes. We also asked whether perturbations in adipose tissue composition and gene expression, if they occur, would be accompanied by reciprocal metabolic changes in the liver. METHODS AND RESULTS: The chylomicronemia in Gpihbp1-/- mice was associated with reduced levels of essential fatty acids in adipose tissue triglycerides and increased expression of lipid biosynthetic genes. The liver exhibited the opposite changes: increased levels of essential fatty acids in triglycerides and reduced expression of lipid biosynthetic genes. CONCLUSIONS: Defective lipolysis in Gpihbp1-/- mice causes reciprocal metabolic perturbations in adipose tissue and liver. In adipose tissue, the essential fatty acid content of triglycerides is reduced and lipid biosynthetic gene expression is increased, whereas the opposite changes occur in the liver.
ESTHER : Weinstein_2012_Arterioscler.Thromb.Vasc.Biol_32_230
PubMedSearch : Weinstein_2012_Arterioscler.Thromb.Vasc.Biol_32_230
PubMedID: 22173228

Title : Chylomicronemia elicits atherosclerosis in mice--brief report - Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_20
Author(s) : Weinstein MM , Yin L , Tu Y , Wang X , Wu X , Castellani LW , Walzem RL , Lusis AJ , Fong LG , Beigneux AP , Young SG
Ref : Arterioscler Thromb Vasc Biol , 30 :20 , 2010
Abstract : OBJECTIVE: The risk of atherosclerosis in the setting of chylomicronemia has been a topic of debate. In this study, we examined susceptibility to atherosclerosis in Gpihbp1-deficient mice (Gpihbp1(-/-)), which manifest severe chylomicronemia as a result of defective lipolysis. METHODS AND RESULTS: Gpihbp1(-/-) mice on a chow diet have plasma triglyceride and cholesterol levels of 2812+/-209 and 319+/-27 mg/dL, respectively. Even though nearly all of the lipids were contained in large lipoproteins (50 to 135 nm), the mice developed progressive aortic atherosclerosis. In other experiments, we found that both Gpihbp1-deficient "apo-B48-only" mice and Gpihbp1-deficient "apo-B100-only" mice manifest severe chylomicronemia. Thus, GPIHBP1 is required for the processing of both apo-B48- and apo-B100-containing lipoproteins. CONCLUSIONS: Chylomicronemia causes atherosclerosis in mice. Also, we found that GPIHBP1 is required for the lipolytic processing of both apo-B48- and apo-B100-containing lipoproteins.
ESTHER : Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_20
PubMedSearch : Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_20
PubMedID: 19815815

Title : Hippocampal AMPA receptor gating controlled by both TARP and cornichon proteins - Kato_2010_Neuron_68_1082
Author(s) : Kato AS , Gill MB , Ho MT , Yu H , Tu Y , Siuda ER , Wang H , Qian YW , Nisenbaum ES , Tomita S , Bredt DS
Ref : Neuron , 68 :1082 , 2010
Abstract : Transmembrane AMPA receptor regulatory proteins (TARPs) and cornichon proteins (CNIH-2/3) independently modulate AMPA receptor trafficking and gating. However, the potential for interactions of these subunits within an AMPA receptor complex is unknown. Here, we find that TARPs gamma-4, gamma-7, and gamma-8, but not gamma-2, gamma-3, or gamma-5, cause AMPA receptors to "resensitize" upon continued glutamate application. With gamma-8, resensitization occurs with all GluA subunit combinations; however, gamma-8-containing hippocampal neurons do not display resensitization. In recombinant systems, CNIH-2 abrogates gamma-8-mediated resensitization and modifies AMPA receptor pharmacology and gating to match that of hippocampal neurons. In hippocampus, gamma-8 and CNIH-2 associate in postsynaptic densities and CNIH-2 protein levels are markedly diminished in gamma-8 knockout mice. Manipulating neuronal CNIH-2 levels modulates the electrophysiological properties of extrasynaptic and synaptic gamma-8-containing AMPA receptors. Thus, gamma-8 and CNIH-2 functionally interact with common hippocampal AMPA receptor complexes to modulate synergistically kinetics and pharmacology.
ESTHER : Kato_2010_Neuron_68_1082
PubMedSearch : Kato_2010_Neuron_68_1082
PubMedID: 21172611

Title : Unexpected expression pattern for glycosylphosphatidylinositol-anchored HDL-binding protein 1 (GPIHBP1) in mouse tissues revealed by positron emission tomography scanning - Olafsen_2010_J.Biol.Chem_285_39239
Author(s) : Olafsen T , Young SG , Davies BS , Beigneux AP , Kenanova VE , Voss C , Young G , Wong KP , Barnes RH, 2nd , Tu Y , Weinstein MM , Nobumori C , Huang SC , Goldberg IJ , Bensadoun A , Wu AM , Fong LG
Ref : Journal of Biological Chemistry , 285 :39239 , 2010
Abstract : Glycosylphosphatidylinositol-anchored high density lipoprotein-binding protein 1 (GPIHBP1), a GPI-anchored endothelial cell protein, binds lipoprotein lipase (LPL) and transports it into the lumen of capillaries where it hydrolyzes triglycerides in lipoproteins. GPIHBP1 is assumed to be expressed mainly within the heart, skeletal muscle, and adipose tissue, the sites where most lipolysis occurs, but the tissue pattern of GPIHBP1 expression has never been evaluated systematically. Because GPIHBP1 is found on the luminal face of capillaries, we predicted that it would be possible to define GPIHBP1 expression patterns with radiolabeled GPIHBP1-specific antibodies and positron emission tomography (PET) scanning. In Gpihbp1(-/-) mice, GPIHBP1-specific antibodies were cleared slowly from the blood, and PET imaging showed retention of the antibodies in the blood pools (heart and great vessels). In Gpihbp1(+/+) mice, the antibodies were cleared extremely rapidly from the blood and, to our surprise, were taken up mainly by lung and liver. Immunofluorescence microscopy confirmed the presence of GPIHBP1 in the capillary endothelium of both lung and liver. In most tissues with high levels of Gpihbp1 expression, Lpl expression was also high, but the lung was an exception (very high Gpihbp1 expression and extremely low Lpl expression). Despite low Lpl transcript levels, however, LPL protein was readily detectable in the lung, suggesting that some of that LPL originates elsewhere and then is captured by GPIHBP1 in the lung. In support of this concept, lung LPL levels were significantly lower in Gpihbp1(-/-) mice than in Gpihbp1(+/+) mice. In addition, Lpl(-/-) mice expressing human LPL exclusively in muscle contained high levels of human LPL in the lung.
ESTHER : Olafsen_2010_J.Biol.Chem_285_39239
PubMedSearch : Olafsen_2010_J.Biol.Chem_285_39239
PubMedID: 20889497

Title : GPIHBP1 is responsible for the entry of lipoprotein lipase into capillaries - Davies_2010_Cell.Metab_12_42
Author(s) : Davies BS , Beigneux AP , Barnes RH, 2nd , Tu Y , Gin P , Weinstein MM , Nobumori C , Nyren R , Goldberg I , Olivecrona G , Bensadoun A , Young SG , Fong LG
Ref : Cell Metab , 12 :42 , 2010
Abstract : The lipolytic processing of triglyceride-rich lipoproteins by lipoprotein lipase (LPL) is the central event in plasma lipid metabolism, providing lipids for storage in adipose tissue and fuel for vital organs such as the heart. LPL is synthesized and secreted by myocytes and adipocytes, but then finds its way into the lumen of capillaries, where it hydrolyzes lipoprotein triglycerides. The mechanism by which LPL reaches the lumen of capillaries has remained an unresolved problem of plasma lipid metabolism. Here, we show that GPIHBP1 is responsible for the transport of LPL into capillaries. In Gpihbp1-deficient mice, LPL is mislocalized to the interstitial spaces surrounding myocytes and adipocytes. Also, we show that GPIHBP1 is located at the basolateral surface of capillary endothelial cells and actively transports LPL across endothelial cells. Our experiments define the function of GPIHBP1 in triglyceride metabolism and provide a mechanism for the transport of LPL into capillaries.
ESTHER : Davies_2010_Cell.Metab_12_42
PubMedSearch : Davies_2010_Cell.Metab_12_42
PubMedID: 20620994

Title : Cholesterol intake modulates plasma triglyceride levels in glycosylphosphatidylinositol HDL-binding protein 1-deficient mice - Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_2106
Author(s) : Weinstein MM , Tu Y , Beigneux AP , Davies BS , Gin P , Voss C , Walzem RL , Reue K , Tontonoz P , Bensadoun A , Fong LG , Young SG
Ref : Arterioscler Thromb Vasc Biol , 30 :2106 , 2010
Abstract : OBJECTIVE: To determine whether plasma triglyceride levels in adult Glycosylphosphatidylinositol HDL-binding protein 1 (GPIHBP1)-deficient (Gpihbp1(-/-)) mice would be sensitive to cholesterol intake. METHODS AND RESULTS: Gpihbp1(-/-) mice were fed a Western diet containing 0.15% cholesterol. After 4 to 8 weeks, their plasma triglyceride levels were 113 to 135 mmol/L. When 0.005% ezetimibe was added to the diet to block cholesterol absorption, Lpl expression in the liver was reduced significantly, and the plasma triglyceride levels were significantly higher (>170 mmol/L). We also assessed plasma triglyceride levels in Gpihbp1(-/-) mice fed Western diets containing either high (1.3%) or low (0.05%) amounts of cholesterol. The high-cholesterol diet significantly increased Lpl expression in the liver and lowered plasma triglyceride levels. CONCLUSIONS: Treatment of Gpihbp1(-/-) mice with ezetimibe lowers Lpl expression in the liver and increases plasma triglyceride levels. A high-cholesterol diet had the opposite effects. Thus, cholesterol intake modulates plasma triglyceride levels in Gpihbp1(-/-) mice.
ESTHER : Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_2106
PubMedSearch : Weinstein_2010_Arterioscler.Thromb.Vasc.Biol_30_2106
PubMedID: 20814015

Title : Hydrolysis and soil sorption of insecticide pyraclofos - Yang_2008_J.Environ.Sci.Health.B_43_219
Author(s) : Yang H , Xue B , Li L , Zhou S , Tu Y , Lin C
Ref : J Environ Sci Health B , 43 :219 , 2008
Abstract : The hydrolysis of the insecticide pyraclofos in buffered solutions at pH 5.0, 7.0 and 9.0, and its sorption on four soils of different physicochemical properties were investigated. The results showed that the degradation of pyraclofos in buffered solutions followed pseudo-first-order kinetics. At 40 degrees C, the rate constants for the hydrolysis of pyraclofos at pH 5.0, 7.0 and 9.0 were 0.0214, 0.1293, and 2.1656 d(-1), respectively. Pyraclofos was relatively stable under both acidic and neutral conditions, while it was readily hydrolyzed under basic conditions. The sorption of pyraclofos on four soils was well described by the Freundlich equation. The sorption constant, K(f), increased with an increase in soil organic carbon content, suggesting that organic carbon content was an important factor affecting sorption. The K(oc) values for Xiaoshan clay loam soil, Hangzhou I clay loam soil, Hangzhou II soil, and Fuyang silt loam soil were 30.4, 6.7, 5.3, and 7.1, respectively. These results suggest that the sorption of pyraclofos on the tested soils was relatively weak.
ESTHER : Yang_2008_J.Environ.Sci.Health.B_43_219
PubMedSearch : Yang_2008_J.Environ.Sci.Health.B_43_219
PubMedID: 18368541

Title : Sequence and analysis of rice chromosome 4 - Feng_2002_Nature_420_316
Author(s) : Feng Q , Zhang Y , Hao P , Wang S , Fu G , Huang Y , Li Y , Zhu J , Liu Y , Hu X , Jia P , Zhao Q , Ying K , Yu S , Tang Y , Weng Q , Zhang L , Lu Y , Mu J , Zhang LS , Yu Z , Fan D , Liu X , Lu T , Li C , Wu Y , Sun T , Lei H , Li T , Hu H , Guan J , Wu M , Zhang R , Zhou B , Chen Z , Chen L , Jin Z , Wang R , Yin H , Cai Z , Ren S , Lv G , Gu W , Zhu G , Tu Y , Jia J , Chen J , Kang H , Chen X , Shao C , Sun Y , Hu Q , Zhang X , Zhang W , Wang L , Ding C , Sheng H , Gu J , Chen S , Ni L , Zhu F , Chen W , Lan L , Lai Y , Cheng Z , Gu M , Jiang J , Li J , Hong G , Xue Y , Han B
Ref : Nature , 420 :316 , 2002
Abstract : Rice is the principal food for over half of the population of the world. With its genome size of 430 megabase pairs (Mb), the cultivated rice species Oryza sativa is a model plant for genome research. Here we report the sequence analysis of chromosome 4 of O. sativa, one of the first two rice chromosomes to be sequenced completely. The finished sequence spans 34.6 Mb and represents 97.3% of the chromosome. In addition, we report the longest known sequence for a plant centromere, a completely sequenced contig of 1.16 Mb corresponding to the centromeric region of chromosome 4. We predict 4,658 protein coding genes and 70 transfer RNA genes. A total of 1,681 predicted genes match available unique rice expressed sequence tags. Transposable elements have a pronounced bias towards the euchromatic regions, indicating a close correlation of their distributions to genes along the chromosome. Comparative genome analysis between cultivated rice subspecies shows that there is an overall syntenic relationship between the chromosomes and divergence at the level of single-nucleotide polymorphisms and insertions and deletions. By contrast, there is little conservation in gene order between rice and Arabidopsis.
ESTHER : Feng_2002_Nature_420_316
PubMedSearch : Feng_2002_Nature_420_316
PubMedID: 12447439
Gene_locus related to this paper: orysa-Q7XTC5 , orysa-Q7F959 , orysa-q7f9i3 , orysa-q7x7y5 , orysa-q7xkj9 , orysa-q7xr62 , orysa-q7xr63 , orysa-q7xr64 , orysa-q7xsg1 , orysa-q7xsq2 , orysa-Q7XTM8 , orysa-q7xts6 , orysa-q7xue7 , orysa-q7xv53 , orysa-Q7XVB5 , orysa-Q7XVG5 , orysj-q0jaf0 , orysj-q7f8x1