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Cytochrome P450 endoplasmic reticulumassociated degradation(ERAD): therapeutic and pathophysiological implications

Acta Pharmaceutica Sinica B 2020年第1期10卷 42-60页

作者： Doyoung Kwon Sung-Mi Kim Maria Almira Correia Department of Cellular and Molecular Pharmacology University of California San FranciscoSan FranciscoCA 94158-2517USA Pharmaceutical Chemistry University of California San FranciscoSan FranciscoCA 94158-2517USA Bioengineering and Therapeutic Sciences University of California San FranciscoSan FranciscoCA 94158-2517USA The Liver Center University of California San FranciscoSan FranciscoCA 94158-2517USA

The hepatic endoplasmic reticulum(ER)-anchored cytochromes P450(P450s)are mixedfunction oxidases engaged in the biotransformation of physiologically relevant endobiotics as well as of myriad xenobiotics of therapeutic and environmental relevance.P450 ER-content and hence function is regulated by their coordinated hemoprotein syntheses and proteolytic *** P450 proteolytic turnover occurs through a process known as ER-associated degradation(ERAD)that involves ubiquitindependent proteasomal degradation(UPD)and/or autophagic-lysosomal degradation(ALD).Herein,on the basis of available literature reports and our own recent findings of in vitro as well as in vivo experimental studies,we discuss the therapeutic and pathophysiological implications of altered P450 ERAD and its plausible clinical *** specifically(i)describe the P450 ERAD-machinery and how it may be repurposed for the generation of antigenic P450 peptides involved in P450 autoantibodypathogenesis in drug-induced acute hypersensitivity reactions and liver injury,or viral hepatitis;(ⅱ)discuss the relevance of accelerated or disrupted P450-ERAD to the pharmacological and/or toxicological effects of clinically relevant P450 drug substrates;and(ⅲ)detail the pathophysiological consequences of disrupted P450 ERAD,contributing to non-alcoholic fatty liver disease(NAFLD)/non-alcoholic steatohepatitis(NASH)under certain synergistic cellular conditions.

关键词： Cytochromes P450 Endoplasmic reticulumassociated degradation CHIP E3 ubiquitin ligase gp78/AMFR E3 ubiquitin ligase JNK1 AMPK1 Non-alcoholic fatty liver disease Non-alcoholic steatohepatitis

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Involvement of phosphatase and tensin homolog-induced putative kinase 1–Parkin-mediated mitophagy in septic acute kidney injury

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Chinese Medical Journal 2019年第19期132卷 2340-2347页

作者： Xin-Gui Dai Wei Xu Tao Li Jia-Ying Lu Yang Yang Qiong Li Zhen-Hua Zeng Yu-Hang Ai Department of Intensive Care Unit Xiangya HospitalCentral South UniversityChangshaHunan 410078China Department of Critical Care Medicine The First People's Hospital of ChenzhouChenzhouHunan 423000China Department of Critical Care Medicine Nanfang HospitalSouthern Medical UniversityGuangzhouGuangdong 510515China

Background:Studies have reported mitophagy activation in renal tubular epithelial cells(RTECs)in acute kidney injury(AKI).Phosphatase and tensin homolog-induced putative kinase 1(PINK1)and E3 ubiquitin-protein ligase Parkin are involved in mitophagy regulation;however,little is known about the role of PINK1-Parkin mitophagy in septic *** we investigated whether the PINK1-Parkin mitophagy pathway is involved in septic AKI and its effects on cell apoptosis in vitro and on renal functions in ***:Mitophagy-related gene expression was determined using Western blot assay in human RTEC cell line HK-2 stimulated with bacterial lipopolysaccharide(LPS)and in RTECs from septic AKI rats induced by cecal ligation and perforation(CLP).Autophagy-related ultrastructural features in rat RTECs were observed using electron ***-and loss-of-function approaches were performed to investigate the role of the PINK1-Parkin pathway in HK-2 cell *** activators and inhibitors were used to assess the effects of mitophagy modulation on cell apoptosis in vitro and on renal functions in ***:LPS stimulation could significantly induce LC3-II and BECN-1 protein expression(LC3-II:1.72±0.05 vs.1.00±0.05,P<0.05;BECN-1:5.33±0.57 vs.1.00±0.14,P<0.05)at 4 h in ***,LC3-II,and BECN-1 protein levels were significantly increased and peaked at 2 h after CLP(LC3-II:3.33±0.12 vs.1.03±0.15,P<0.05;BECN-1:1.57±0.26 vs.1.02±0.11,P<0.05)in vivo compared with those after sham *** deformation and mitolysosome-mediated mitochondria clearance were observed in RTECs from septic ***1 knockdown significantly attenuated LC3-II protein expression(1.35±0.21 vs.2.38±0.22,P<0.05),whereas PINK1 overexpression markedly enhanced LC3-II protein expression(2.07±0.21 vs.1.29±0.19,P<0.05)compared with LPS-stimulated HK-2 ***-induced proapoptotic protein expression remained unchanged in autophagy activator-treated HK-2 cells and was significantl

关键词： Sepsis Acute kidney injury Autophagy Mitophagy Phosphatase and tensin homolog-induced putative kinase 1 E3 ubiquitin-protein ligase Parkin

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Real time monitoring of nucleic acids ligation based on molecular beacon

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Chinese Science Bulletin 2003年第12期48卷 1215-1218页

作者： Zhiwen Tang Kemin Wang Weihong Tan Jun Li Lingfeng Liu Qiuping Guo Xiangxian Meng Shasheng Huang Du Li Weifang Luo Hunan Univ Coll Chem & Chem Engn Inst Biol Technol State Key Lab Chemobiosensing & Chemometr Changsha 410082 Peoples R China

A novel method has been developed to monitor the nucleic acids ligation process. Molecular beacon was employed here to convert the ligation information into fluo-rescence signal quickly and quantitatively. This method pro-vides effective and original approach to researching the dy-namic ligation process and the interactions between nucleic acids and ligase. An analytical method for T4 DNA ligase based on this way has been built up with a linear detection range from 2.3×10-4 U/mL to 0.23 U/mL. It is rapid and sensitive to detect 2.8×10-5 U T4 DNA ligase in 10 min.

关键词： nucleic acids ligation T4 DNA ligase real time assay molecular beacon.

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Regulation of NLR stability in plant immunity

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Frontiers of Agricultural Science and Engineering 2019年第2期6卷 97-104页

作者： Tao WANG Jiaxin LI Qian-Hua SHEN State Key Laboratory of Plant Cell and Chromosome Engineering/Institute of Genetics and Developmental Biology Chinese Academy of Sciences Beijing 100101 China Eberly College of Science The Pennsylvania State University University Park PA 16802 USA

Plant nucleotide binding domain and leucinerich repeat (NLR) receptors recognize pathogen effectors directly or indirectly and mediate innate immune responses. NLR-mediated immunity also has direct impacts on plant growth and development, as well as yield and survival. The levels of NLR proteins are therefore intricately controlled in plants to balance defense responses and other processes. In recent years, the ubiquitination-26S proteasome system and the HSP90 chaperones have emerged as having key functions in the regulation of NLR stability. The N-end rule pathway of protein degradation is also directly linked to NLR stability. Recent progress in the regulation of NLR stability and turnover is summarized here, focusing on the key components and pathways.

关键词： E3 ubiquitin ligase degradation nucleotidebinding leucine-rich repeat receptor plant immunity proteasome protein stability ubiquitination

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Infected cell protein 0 functional domains and their coordination in herpes simplex virus replication

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World Journal of Virology 2016年第1期5卷 1-13页

作者： Haidong Gu Department of Biological Sciences Wayne State University

Herpes simplex virus 1(HSV-1) is a ubiquitous human pathogen that establishes latent infection in ganglia neurons. Its unique life cycle requires a balanced "conquer and compromise" strategy to deal with the host anti-viral defenses. One of HSV-1 α(immediate early) gene products, infected cell protein 0(ICP0), is a multifunctional protein that interacts with and modulates a wide range of cellular defensive pathways. These pathways may locate in different cell compartments, which then migrate or exchange factors upon stimulation, for the purpose of a concerted and effective defense. ICP0 is able to simultaneously attack multiple host pathways by either degrading key restrictive factors or modifying repressive complexes. This is a viral protein that contains an E3 ubiquitin ligase, translocates among different cell compartments and interacts with major defensive complexes. The multiple functional domains of ICP0 can work independently and at the same time coordinate with each other. Dissecting the functional domains of ICP0 and delineating the coordination of these domains will help us understand HSV-1 pathogenicity as well as host defense mechanisms. This article focuses on describing individual ICP0 domains, their biochemical properties and their implication in HSV-1 infection. By putting individual domain functions back into the picture of host anti-viral defense network, this review seeks to elaborate the complex interactions between HSV-1 and its host.

关键词： Subcellular translocation Herpes simplex virus 1 Infected cell protein 0 E3 ubiquitin ligase Protein modification ND10 nuclear bodies Chromatin repression

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SYNTHESIS OF THE 5'-HALF MOLECULE PENTATRIACONTANUCLEOTIDE (35p) OF YEAST ALANINE TRANSFER RIBONUCLEIC ACID

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Chinese Science Bulletin 1984年第1期29卷 109-115页

作者：陈海宝庄建华陈雅娣胡美浩 Shanghai Institute of Organic Chemistry Academia Sinica Shanghai Institute of Cell Biology Academia Sinica Department of Biology Peking University

After the completion of the synthesis of the 3?-half molecule of yeast alanine transfer RNA (tRNAyAla) and that of the three large oligonucleotide fragments [Ⅰ, Ⅱ and Ⅲ] （Fig. 1） corresponding to the 5’-half molecule of tRNAyAla, i.e. pentatriacontanucleotide （1—35）, we started to synthesize the 5’-half molecule. In order to get necessary preinformation about the behavior of T4 RNA ligase in joining the three oligonucleotide intermediates, two different routes （A and B） of synthesis

关键词： tRNA yeast completion joining ligase alanine ACID synthesize amide ligation

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***

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外科研究与新技术 1992年第2期 73-74页

920233 Cloning of the sequences of kineto-plast DNA specific to Leishmania donovanispecies and *** Honggong (吕洪刚),HUXiaosu (胡孝素).Lab Parasitol,West-China *** J Parasitol & Parasit Dis 1991;9(4):*** identify the ... 详细信息

关键词：胡孝素 DNA 吕洪 plast heterogeneous Cloning inserted ligase immunized isolates

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Relationship between glucokinase gene 6 tag single nucleotide polymorphism sites and type 2 diabetes mellitus

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China Medical Abstracts(Internal Medicine) 2016年第1期33卷 3-4页

作者：张秀明 Dept Exam Med Center Zhongshan Affil HospSun Yatsen Univ

Objective To investigate the relationships between glucokinase(GCK)gene 6(tag single-nucleotide polymorphisms,tag SNPs)sites which named rs12702070,rs2971672,rs2268569,rs2268573,rs2300587 and rs1476891 polymorphisms a... 详细信息

关键词： SNPs allele recessive genotype linkage Genotype susceptibility haplotype ligase signed

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TOTAL SYNTHESIS OF YEAST ALANINE TRANSFER RIBONUCLEIC ACID

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Chinese Science Bulletin 1982年第2期27卷 216-219页

作者： Shanghai Institute of Biochemistry, Academia Sinica Shanghai Institute of Cell Biology, Academia Siniva Shanghai Institute of Organic Chemistry, Academia Sinica Institute of Biophysics, Academia Sinica Department of Biology, Peking University and Shanghai No. 2 Reagent Factory

In October of 1979, we reported the syntheses of three oligonucleotide fragments of the 3’-half molecule (corresponding to nucleotides 36—45, 46—57 and 58—76 respectively) of yeast alanine tRNA in the PRC-FRG Join... 详细信息

关键词： yeast tRNA alanine Proteins ACID ligase ligation donor 巴口吧刀

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STUDIES ON ENZYMATIC SYNTHESIS OF OLIGORIBONUCLEOTIDES ON SOLID SUPPORT

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Chinese Science Bulletin 1981年第4期26卷 346-350页

作者：王启松商金宝包俊茹 Shanghai Institute of Biochemistry Academia Sinica

Since the availability of T4 RNA ligase, a great progress has been made in fields of synthesis of polynueleotides. However, all reactions were carried out in solvents. Though reactions in solvents favour the activity of enzyme, there still exist certain drawbacks, for instance, it takes a long time for separation and the recovery is

关键词： instance SOLID availability ligase RNA eliminating spots alkaline donor ammonia

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