Liao Z

References (11)

Title : Carboxyl-terminal sequences in APOA5 are important for suppressing ANGPTL3\/8 activity - Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
Author(s) : Chen YQ , Yang Y , Zhen EY , Beyer TP , Li H , Wen Y , Ehsani M , Jackson N , Xie K , Jung H , Scheithauer JL , Kumari A , Birrane G , Russell AM , Balasubramaniam D , Liao Z , Siegel RW , Qian Y , Ploug M , Young SG , Konrad RJ
Ref : Proc Natl Acad Sci U S A , 121 :e2322332121 , 2024
Abstract : Apolipoprotein AV (APOA5) lowers plasma triglyceride (TG) levels by binding to the angiopoietin-like protein 3/8 complex (ANGPTL3/8) and suppressing its capacity to inhibit lipoprotein lipase (LPL) catalytic activity and its ability to detach LPL from binding sites within capillaries. However, the sequences in APOA5 that are required for suppressing ANGPTL3/8 activity have never been defined. A clue to the identity of those sequences was the presence of severe hypertriglyceridemia in two patients harboring an APOA5 mutation that truncates APOA5 by 35 residues ("APOA5delta35"). We found that wild-type (WT) human APOA5, but not APOA5delta35, suppressed ANGPTL3/8's ability to inhibit LPL catalytic activity. To pursue that finding, we prepared a mutant mouse APOA5 protein lacking 40 C-terminal amino acids ("APOA5delta40"). Mouse WT-APOA5, but not APOA5delta40, suppressed ANGPTL3/8's capacity to inhibit LPL catalytic activity and sharply reduced plasma TG levels in mice. WT-APOA5, but not APOA5delta40, increased intracapillary LPL levels and reduced plasma TG levels in Apoa5(-/-) mice (where TG levels are high and intravascular LPL levels are low). Also, WT-APOA5, but not APOA5delta40, blocked the ability of ANGPTL3/8 to detach LPL from cultured cells. Finally, an antibody against a synthetic peptide corresponding to the last 26 amino acids of mouse APOA5 reduced intracapillary LPL levels and increased plasma TG levels in WT mice. We conclude that C-terminal sequences in APOA5 are crucial for suppressing ANGPTL3/8 activity in vitro and for regulating intracapillary LPL levels and plasma TG levels in vivo.
ESTHER : Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
PubMedSearch : Chen_2024_Proc.Natl.Acad.Sci.U.S.A_121_e2322332121
PubMedID: 38625948
Gene_locus related to this paper: human-LPL

Title : Exploring the enigmatic association between PNLIP variants and risk of chronic pancreatitis in a large Chinese cohort - Cassidy_2024_Pancreatology__
Author(s) : Cassidy BM , Jiang F , Lin J , Chen JM , Curry GE , Ma GX , Wilhelm SJ , Deng SJ , Zhu G , Liao Z , Lowe ME , Xiao XK , Zou WB
Ref : Pancreatology , : , 2024
Abstract : BACKGROUND & AIMS: Protease-sensitive PNLIP variants were recently associated with chronic pancreatitis (CP) in European populations. The pathological mechanism yet remains elusive. Herein, we performed a comprehensive genetic and functional analysis of PNLIP variants found in a large Chinese cohort, aiming to further unravel the enigmatic association of PNLIP variants with CP. METHODS: All coding and flanking intronic regions of the PNLIP gene were analyzed for rare variants by targeted next-generation sequencing in 1082 Chinese CP patients and 1196 controls. All novel missense variants were subject to analysis of secretion, lipase activity, and proteolytic degradation. One variant was further analyzed for its potential to misfold and induce endoplasmic reticulum (ER) stress. p.F300L, the most common PNLIP variant associated with CP, was used as a control. RESULTS: We identified 12 rare heterozygous PNLIP variants, with 10 being novel. The variant carrier frequency did not differ between the groups. Of them, only the variant p.A433T found in a single patient was considered pathologically relevant. p.A433T exhibited increased susceptibility to proteolytic degradation, which was much milder than p.F300L. Interestingly, both variants exhibited an increased tendency to misfold, leading to intracellular retention as insoluble aggregates, reduced secretion, and elevated ER stress. CONCLUSIONS: Our genetic and functional analysis of PNLIP variants identified in a Chinese CP cohort suggests that the p.A433T variant and the previously identified p.F300L variant are not only protease-sensitive but also may be potentially proteotoxic. Mouse studies of the PNLIP p.F300L and p.A433T variants are needed to clarify their role in CP.
ESTHER : Cassidy_2024_Pancreatology__
PubMedSearch : Cassidy_2024_Pancreatology__
PubMedID: 38485544

Title : The CEL-HYB1 Hybrid Allele Promotes Digestive Enzyme Misfolding and Pancreatitis in Mice - Mao_2022_Cell.Mol.Gastroenterol.Hepatol__
Author(s) : Mao XT , Zou WB , Cao Y , Wang YC , Deng SJ , Cooper DN , Ferec C , Li ZS , Chen JM , Liao Z
Ref : Cell Mol Gastroenterol Hepatol , : , 2022
Abstract : BACKGROUND & AIMS: A hybrid allele that originated from homologous recombination between CEL and its pseudogene (CELP), CEL-HYB1 increases the risk of chronic pancreatitis (CP). Although suggested to cause digestive enzyme misfolding, definitive in vivo evidence for this postulate has been lacking. METHODS: CRISPR-Cas9 was used to generate humanized mice harboring the CEL-HYB1 allele on a C57BL/6J background. Humanized CEL mice and C57BL/6J mice were used as controls. Pancreata were collected and analyzed by histology, immunohistochemistry, immunoblotting and transcriptomics. Isolated pancreatic acini were cultured in vitro to measure the secretion and aggregation of CEL-HYB1. Mice were given caerulein injections to induce acute pancreatitis (AP) and CP. RESULTS: Pancreata from mice expressing CEL-HYB1 developed pathological features characteristic of focal pancreatitis that included acinar atrophy and vacuolization, inflammatory infiltrates and fibrosis in a time-dependent manner. CEL-HYB1 expression in pancreatic acini led to decreased secretion and increased intracellular aggregation, and triggered endoplasmic reticulum stress compared with CEL. The autophagy levels of pancreata from mice expressing CEL-HYB1 changed at different developmental stages; some aged CEL-HYB1 mice exhibited an accumulation of large autophagic vesicles and impaired autophagy in acinar cells. Administration of caerulein increased the severity of AP/CP in mice expressing CEL-HYB1 compared to control mice, accompanied by higher levels of endoplasmic reticulum stress. CONCLUSIONS: Expression of a humanized form of CEL-HYB1 in mice promotes endoplasmic reticulum stress and pancreatitis through a misfolding-dependent pathway. Impaired autophagy appears to be involved in the pancreatic injury in aged CEL-HYB1 mice. These mice have the potential to be used as a model to identify therapeutic targets for CP.
ESTHER : Mao_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedSearch : Mao_2022_Cell.Mol.Gastroenterol.Hepatol__
PubMedID: 35398595

Title : Phytophthora infestans Ago1-associated miRNA promotes potato late blight disease - Hu_2021_New.Phytol__
Author(s) : Hu X , Persson Hoden K , Liao Z , sman A , Dixelius C
Ref : New Phytol , : , 2021
Abstract : Phytophthora spp. incite serious plant damages by exploiting a large number of effector proteins and small RNAs (sRNAs). Several reports are describing modulation of host RNA biogenesis and defence gene expression. Here, we analysed Phytophthora infestans Argonaute (Ago) 1 associated small RNAs during potato leaf infection. sRNAs were co-immunoprecipitated, deep sequenced and analysed against the P. infestans and potato genomes, followed by transcript analyses and transgenic assays on a predicted target. Extensive targeting of potato and pathogen-derived sRNAs to a range of mRNAs was observed, including 638 sequences coding for resistance (R) proteins in the host genome. The single miRNA encoded by P. infestans (miR8788) was found to target a potato alpha/beta hydrolase-type encoding gene (StABH1), a protein localized to the plasma membrane. Analyses of stable transgenic potato lines harbouring overexpressed StABH1 or artificial miRNA gene constructs demonstrated the importance of StABH1 during infection by P. infestans. miR8788 knock-down strains showed reduced growth on potato. In analogy, elevated StABH1 expression levels were observed when inoculated with the two knock-down strains compared to the wild-type strain 88069. The data suggest that sRNA encoded by P. infestans can affect potato mRNA, and thereby expand its already known multifaceted strategies to facilitate infection.
ESTHER : Hu_2021_New.Phytol__
PubMedSearch : Hu_2021_New.Phytol__
PubMedID: 34605025
Gene_locus related to this paper: soltu-m1acp5 , arath-At1g10740

Title : Characterization of CEL-DUP2: Complete duplication of the carboxyl ester lipase gene is unlikely to influence risk of chronic pancreatitis - Fjeld_2020_Pancreatology__
Author(s) : Fjeld K , Masson E , Lin JH , Michl P , Stokowy T , Gravdal A , El Jellas K , Steine SJ , Hoem D , Johansson BB , Dalva M , Ruffert C , Zou WB , Li ZS , Njolstad PR , Chen JM , Liao Z , Johansson S , Rosendahl J , Ferec C , Molven A
Ref : Pancreatology , : , 2020
Abstract : BACKGROUND/OBJECTIVES: Carboxyl ester lipase is a pancreatic enzyme encoded by CEL, an extremely polymorphic human gene. Pathogenic variants of CEL either increases the risk for chronic pancreatitis (CP) or cause MODY8, a syndrome of pancreatic exocrine and endocrine dysfunction. Here, we aimed to characterize a novel duplication allele of CEL (CEL-DUP2) and to investigate whether it associates with CP or pancreatic cancer. METHODS: The structure of CEL-DUP2 was determined by a combination of Sanger sequencing, DNA fragment analysis, multiplex ligation-dependent probe amplification and whole-genome sequencing. We developed assays for screening of CEL-DUP2 and analyzed cohorts of idiopathic CP, alcoholic CP and pancreatic cancer. CEL protein expression was analyzed by immunohistochemistry. RESULTS: CEL-DUP2 consists of an extra copy of the complete CEL gene. The allele has probably arisen from non-allelic, homologous recombination involving the adjacent pseudogene of CEL. We found no association between CEL-DUP2 carrier frequency and CP in cohorts from France (cases/controls: 2.5%/2.4%; P = 1.0), China (10.3%/8.1%; P = 0.08) or Germany (1.6%/2.3%; P = 0.62). Similarly, no association with disease was observed in alcohol-induced pancreatitis (Germany: 3.2%/2.3%; P = 0.51) or pancreatic cancer (Norway; 2.5%/3.2%; P = 0.77). Notably, the carrier frequency of CEL-DUP2 was more than three-fold higher in Chinese compared with Europeans. CEL protein expression was similar in tissues from CEL-DUP2 carriers and controls. CONCLUSIONS: Our results support the contention that the number of CEL alleles does not influence the risk of pancreatic exocrine disease. Rather, the pathogenic CEL variants identified so far involve exon 11 sequence changes that substantially alter the protein's tail region.
ESTHER : Fjeld_2020_Pancreatology__
PubMedSearch : Fjeld_2020_Pancreatology__
PubMedID: 32007358

Title : Strigolactone promotes cytokinin degradation through transcriptional activation of CYTOKININ OXIDASE\/DEHYDROGENASE 9 in rice - Duan_2019_Proc.Natl.Acad.Sci.U.S.A_116_14319
Author(s) : Duan J , Yu H , Yuan K , Liao Z , Meng X , Jing Y , Liu G , Chu J , Li J
Ref : Proc Natl Acad Sci U S A , 116 :14319 , 2019
Abstract : Strigolactones (SLs), a group of terpenoid lactones derived from carotenoids, are plant hormones that control numerous aspects of plant development. Although the framework of SL signaling that the repressor DWARF 53 (D53) could be SL-dependently degraded via the SL receptor D14 and F-box protein D3 has been established, the downstream response genes to SLs remain to be elucidated. Here we show that the cytokinin (CK) content is dramatically increased in shoot bases of the rice SL signaling mutant d53 By examining transcript levels of all the CK metabolism-related genes after treatment with SL analog GR24, we identified CYTOKININ OXIDASE/DEHYDROGENASE 9 (OsCKX9) as a primary response gene significantly up-regulated within 1 h of treatment in the wild type but not in d53 We also found that OsCKX9 functions as a cytosolic and nuclear dual-localized CK catabolic enzyme, and that the overexpression of OsCKX9 suppresses the browning of d53 calli. Both the CRISPR/Cas9-generated OsCKX9 mutants and OsCKX9-overexpressing transgenic plants showed significant increases in tiller number and decreases in plant height and panicle size, suggesting that the homeostasis of OsCKX9 plays a critical role in regulating rice shoot architecture. Moreover, we identified the CK-inducible rice type-A response regulator OsRR5 as the secondary SL-responsive gene, whose expression is significantly repressed after 4 h of GR24 treatment in the wild type but not in osckx9 These findings reveal a comprehensive plant hormone cross-talk in which SL can induce the expression of OsCKX9 to down-regulate CK content, which in turn triggers the response of downstream genes.
ESTHER : Duan_2019_Proc.Natl.Acad.Sci.U.S.A_116_14319
PubMedSearch : Duan_2019_Proc.Natl.Acad.Sci.U.S.A_116_14319
PubMedID: 31235564

Title : Acetylcholinesterase is not a generic marker of extracellular vesicles - Liao_2019_J.Extracell.Vesicles_8_1628592
Author(s) : Liao Z , Jaular LM , Soueidi E , Jouve M , Muth DC , Schoyen TH , Seale T , Haughey NJ , Ostrowski M , Thery C , Witwer KW
Ref : J Extracell Vesicles , 8 :1628592 , 2019
Abstract : Acetylcholinesterase (AChE) activity is found in abundance in reticulocytes and neurons and was developed as a marker of reticulocyte EVs in the 1970s. Easily, quickly, and cheaply assayed, AChE activity has more recently been proposed as a generic marker for small extracellular vesicles (sEV) or exosomes, and as a negative marker of HIV-1 virions. To evaluate these proposed uses of AChE activity, we examined data from different EV and virus isolation methods using T-lymphocytic (H9, PM1 and Jurkat) and promonocytic (U937) cell lines grown in culture conditions that differed by serum content. When EVs were isolated by differential ultracentrifugation, no correlation between AChE activity and particle count was observed. AChE activity was detected in non-conditioned medium when serum was added, and most of this activity resided in soluble fractions and could not be pelleted by centrifugation. The serum-derived pelletable AChE protein was not completely eliminated from culture medium by overnight ultracentrifugation; however, a serum "extra-depletion" protocol, in which a portion of the supernatant was left undisturbed during harvesting, achieved near-complete depletion. In conditioned medium also, only small percentages of AChE activity could be pelleted together with particles. Furthermore, no consistent enrichment of AChE activity in sEV fractions was observed. Little if any AChE activity is produced by the cells we examined, and this activity was mainly present in non-vesicular structures, as shown by electron microscopy. Size-exclusion chromatography and iodixanol gradient separation showed that AChE activity overlaps only minimally with EV-enriched fractions. AChE activity likely betrays exposure to blood products and not EV abundance, echoing the MISEV 2014 and 2018 guidelines and other publications. Additional experiments may be merited to validate these results for other cell types and biological fluids other than blood.
ESTHER : Liao_2019_J.Extracell.Vesicles_8_1628592
PubMedSearch : Liao_2019_J.Extracell.Vesicles_8_1628592
PubMedID: 31303981

Title : The Genome of Artemisia annua Provides Insight into the Evolution of Asteraceae Family and Artemisinin Biosynthesis - Shen_2018_Mol.Plant_11_776
Author(s) : Shen Q , Zhang L , Liao Z , Wang S , Yan T , Shi P , Liu M , Fu X , Pan Q , Wang Y , Lv Z , Lu X , Zhang F , Jiang W , Ma Y , Chen M , Hao X , Li L , Tang Y , Lv G , Zhou Y , Sun X , Brodelius PE , Rose JKC , Tang K
Ref : Mol Plant , 11 :776 , 2018
Abstract : Artemisia annua, commonly known as sweet wormwood or Qinghao, is a shrub native to China and has long been used for medicinal purposes. A. annua is now cultivated globally as the only natural source of a potent anti-malarial compound, artemisinin. Here, we report a high-quality draft assembly of the 1.74-gigabase genome of A. annua, which is highly heterozygous, rich in repetitive sequences, and contains 63 226 protein-coding genes, one of the largest numbers among the sequenced plant species. We found that, as one of a few sequenced genomes in the Asteraceae, the A. annua genome contains a large number of genes specific to this large angiosperm clade. Notably, the expansion and functional diversification of genes encoding enzymes involved in terpene biosynthesis are consistent with the evolution of the artemisinin biosynthetic pathway. We further revealed by transcriptome profiling that A. annua has evolved the sophisticated transcriptional regulatory networks underlying artemisinin biosynthesis. Based on comprehensive genomic and transcriptomic analyses we generated transgenic A. annua lines producing high levels of artemisinin, which are now ready for large-scale production and thereby will help meet the challenge of increasing global demand of artemisinin.
ESTHER : Shen_2018_Mol.Plant_11_776
PubMedSearch : Shen_2018_Mol.Plant_11_776
PubMedID: 29703587
Gene_locus related to this paper: artan-a0a2u1ns65 , artan-a0a2u1nuf0 , artan-a0a2u1pw87 , artan-a0a2u1ql98 , artan-a0a2u1n9p7.2 , artan-a0a2u1ky94 , artan-a0a2u1pvq0 , artan-a0a2u1q8x4 , artan-a0a2u1mtd1 , artan-a0a2u1l9j8 , artan-a0a2u1lak5 , artan-a0a2u1lfl1 , artan-a0a2u1lzs1 , artan-a0a2u1m5v6 , artan-a0a2u1n4s5 , artan-a0a2u1qgg7

Title : Comparative proteomic analysis of Ulva prolifera response to high temperature stress - Fan_2018_Proteome.Sci_16_17
Author(s) : Fan M , Sun X , Liao Z , Wang J , Li Y , Xu N
Ref : Proteome Sci , 16 :17 , 2018
Abstract : Background: Ulva prolifera belongs to green macroalgae and is the dominant species of green tide. It is distributed worldwide and is therefore subject to high-temperature stress during the growth process. However, the adaptation mechanisms of the response of U. prolifera to high temperatures have not been clearly investigated yet. Methods: In this study, isobaric tags for relative and absolute quantitation (iTRAQ) labelling was applied in combination with the liquid chromatography-tandem mass spectrometry (LC-MS/MS) to conduct comparative proteomic analysis of the response of U. prolifera to high-temperature stress and to elucidate the involvement of this response in adaptation mechanisms. Differentially expressed proteins (DEPs) of U. prolifera under high temperature (denote UpHT) compared with the control (UpC) were identified. Bioinformatic analyses including GO analysis, pathway analysis, and pathway enrichment analysis was performed to analyse the key metabolic pathways that underlie the thermal tolerance mechanism through protein networks. Quantitative real-time PCR and western blot were performed to validate selected proteins. Results: In the present study, 1223 DEPs were identified under high temperature compared with the control, which included 790 up-regulated and 433 down-regulated proteins. The high-temperature stimulus mainly induced the expression of glutathione S-transferase, heat shock protein, ascorbate peroxidase, manganese superoxide dismutase, ubiquitin-related protein, lhcSR, rubisco activase, serine/threonine protein kinase 2, adenylate kinase, Ca(2+)-dependent protein kinase (CDPK), disease resistance protein EDS1, metacaspase type II, NDPK2a, 26S proteasome regulatory subunit, ubiquinone oxidoreductase, ATP synthase subunit, SnRK2s, and cytochrome P450. The down-regulated proteins were photosynthesis-related proteins, glutathione reductase, catalase-peroxidase, thioredoxin, thioredoxin peroxidase, PP2C, and carbon fixation-related proteins. Furthermore, biological index analysis indicated that protein content and SOD activity decreased; the value of Fv/Fm dropped to the lowest point after culture for 96 h. However, APX activity and MDA content increased under high temperature. Conclusion: The present study implied an increase in proteins that were associated with the stress response, oxidative phosphorylation, the cytokinin signal transduction pathway, the abscisic acid signal transduction pathway, and the glutathione metabolism pathway. Proteins that were associated with photosynthesis, carbon fixation in photosynthesis organisms, and the photosynthesis antenna protein pathway were decreased. These pathways played a pivotal role in high temperature regulation. These novel proteins provide a good starting point for further research into their functions using genetic or other approaches. These findings significantly improve the understanding of the molecular mechanisms involved in the tolerance of algae to high-temperature stress.
ESTHER : Fan_2018_Proteome.Sci_16_17
PubMedSearch : Fan_2018_Proteome.Sci_16_17
PubMedID: 30386183

Title : No Association Between CEL-HYB Hybrid Allele and Chronic Pancreatitis in Asian Populations - Zou_2016_Gastroenterology_150_1558
Author(s) : Zou WB , Boulling A , Masamune A , Issarapu P , Masson E , Wu H , Sun XT , Hu LH , Zhou DZ , He L , Fichou Y , Nakano E , Hamada S , Kakuta Y , Kume K , Isayama H , Paliwal S , Mani KR , Bhaskar S , Cooper DN , Ferec C , Shimosegawa T , Chandak GR , Chen JM , Li ZS , Liao Z
Ref : Gastroenterology , 150 :1558 , 2016
Abstract : A hybrid allele between the carboxyl ester lipase gene (CEL) and its pseudogene, CELP (called CEL-HYB), generated by nonallelic homologous recombination between CEL intron 10 and CELP intron 10', was found to increase susceptibility to chronic pancreatitis in a case-control study of patients of European ancestry. We attempted to replicate this finding in 3 independent cohorts from China, Japan, and India, but failed to detect the CEL-HYB allele in any of these populations. The CEL-HYB allele might therefore be an ethnic-specific risk factor for chronic pancreatitis. An alternative hybrid allele (CEL-HYB2) was identified in all 3 Asian populations (1.7% combined carrier frequency), but was not associated with chronic pancreatitis.
ESTHER : Zou_2016_Gastroenterology_150_1558
PubMedSearch : Zou_2016_Gastroenterology_150_1558
PubMedID: 26946345

Title : Schisandrin C Ameliorates Learning and Memory Deficits by Abeta(1-42) -induced Oxidative Stress and Neurotoxicity in Mice - Mao_2015_Phytother.Res_29_1373
Author(s) : Mao X , Liao Z , Guo L , Xu X , Wu B , Xu M , Zhao X , Bi K , Jia Y
Ref : Phytother Res , 29 :1373 , 2015
Abstract : Schisandrin C (SCH-C) is a main and typical antioxidative lignan isolated from the fruits of Schisandra chinensis (Trucz.) Baill (a widely used traditional Chinese medicine). The present study aimed to characterize the effect of SCH-C on memory impairment and further research on pathological changes in Abeta(1-42) -induced Alzheimer's disease mice. Mice were administration with SCH-C daily for 5 days in the lateral cerebral ventricles using sterotaxically implanted cannula. Cognitive functions were assessed by Y-maze test, active avoidance test and Morris water maze test in all groups, and the level of Abeta(1-42) and neuronal injury induced by Abeta(1-42) were reversed remarkably following SCH-C treatment compared with sham group; meanwhile the impairment of short-term or working memory was dramatically improved. In addition, SCH-C significantly inhibited total cholinesterase (ChEtotal), and increased superoxide dismutase (SOD) and glutathione peroxidase (GSH-px) activity glutathione (GSH) levels in the hippocampus and cerebral cortex. It can be speculated that SCH-C offers protection against Abeta(1-42) -induced dysfunction in learning and memory by inhibiting ChEtotal and its antioxidant action. Copyright 2015 John Wiley & Sons, Ltd.
ESTHER : Mao_2015_Phytother.Res_29_1373
PubMedSearch : Mao_2015_Phytother.Res_29_1373
PubMedID: 26074330