10 results on '"Jian, Yuan"'
Search Results
2. Sequencing of 19,219 exomes identifies a low-frequency variant in FKBP5 promoter predisposing to high myopia in a Han Chinese population
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Jianzhong Su, Jian Yuan, Liangde Xu, Shilai Xing, Mengru Sun, Yinghao Yao, Yunlong Ma, Fukun Chen, Longda Jiang, Kai Li, Xiangyi Yu, Zhengbo Xue, Yaru Zhang, Dandan Fan, Ji Zhang, Hui Liu, Xinting Liu, Guosi Zhang, Hong Wang, Meng Zhou, Fan Lyu, Gang An, Xiaoguang Yu, Yuanchao Xue, Jian Yang, and Jia Qu
- Subjects
CP: Genomics ,Biology (General) ,QH301-705.5 - Abstract
Summary: High myopia (HM) is one of the leading causes of visual impairment and blindness worldwide. Here, we report a whole-exome sequencing (WES) study in 9,613 HM cases and 9,606 controls of Han Chinese ancestry to pinpoint HM-associated risk variants. Single-variant association analysis identified three newly identified -genetic loci associated with HM, including an East Asian ancestry-specific low-frequency variant (rs533280354) in FKBP5. Multi-ancestry meta-analysis with WES data of 2,696 HM cases and 7,186 controls of European ancestry from the UK Biobank discerned a newly identified European ancestry-specific rare variant in FOLH1. Functional experiments revealed a mechanism whereby a single G-to-A transition at rs533280354 disrupted the binding of transcription activator KLF15 to the promoter of FKBP5, resulting in decreased transcription of FKBP5. Furthermore, burden tests showed a significant excess of rare protein-truncating variants among HM cases involved in retinal blood vessel morphogenesis and neurotransmitter transport.
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- 2023
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3. Nuclear ATR lysine-tyrosylation protects against heart failure by activating DNA damage response
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Rui Zhao, Ke Cai, Jing-Jing Yang, Qian Zhou, Wei Cao, Jie Xiang, Yi-Hui Shen, Lei-Lei Cheng, Wei-Dong Zang, Yan Lin, Yi-Yuan Yuan, Wei Xu, Hui Tao, Shi-Min Zhao, and Jian-Yuan Zhao
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CP: Molecular biology ,Biology (General) ,QH301-705.5 - Abstract
Summary: Dysregulated amino acid increases the risk for heart failure (HF) via unclear mechanisms. Here, we find that increased plasma tyrosine and phenylalanine levels are associated with HF. Increasing tyrosine or phenylalanine by high-tyrosine or high-phenylalanine chow feeding exacerbates HF phenotypes in transverse aortic constriction and isoproterenol infusion mice models. Knocking down phenylalanine dehydrogenase abolishes the effect of phenylalanine, indicating that phenylalanine functions by converting to tyrosine. Mechanistically, tyrosyl-tRNA synthetase (YARS) binds to ataxia telangiectasia and Rad3-related gene (ATR), catalyzes lysine tyrosylation (K-Tyr) of ATR, and activates the DNA damage response (DDR) in the nucleus. Increased tyrosine inhibits the nuclear localization of YARS, inhibits the ATR-mediated DDR, accumulates DNA damage, and elevates cardiomyocyte apoptosis. Enhancing ATR K-Tyr by overexpressing YARS, restricting tyrosine, or supplementing tyrosinol, a structural analog of tyrosine, promotes YARS nuclear localization and alleviates HF in mice. Our findings implicate facilitating YARS nuclear translocation as a potential preventive and/or interfering measure against HF.
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- 2023
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4. Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair
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Dan Wang, Rui Zhao, Yuan-Yuan Qu, Xin-Yu Mei, Xuan Zhang, Qian Zhou, Yang Li, Shao-Bo Yang, Zhi-Gui Zuo, Yi-Ming Chen, Yan Lin, Wei Xu, Chao Chen, Shi-Min Zhao, and Jian-Yuan Zhao
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Biology (General) ,QH301-705.5 - Abstract
Summary: Colorectal cancer (CRC) onset is profoundly affected by Western diet. Here, we report that high-fat (HF) diet-induced, organ-specific colonic lysine homocysteinylation (K-Hcy) increase might promote CRC onset by impeding DNA damage repair. HF chow induced elevated methionyl-tRNA synthetase (MARS) expression and K-Hcy levels and DNA damage accumulation in the mouse and rat colon, resulting in a phenotype identical to that of CRC tissues. Moreover, the increased copy number of MARS, whose protein product promotes K-Hcy, correlated with increased CRC risk in humans. Mechanistically, MARS preferentially bound to and modified ataxia-telangiectasia and Rad3-related protein (ATR), inhibited ATR and its downstream effectors checkpoint kinase-1 and p53, and relieved cell-cycle arrest and decreased DNA damage-induced apoptosis by disrupting the binding of ATR-interacting protein to ATR. Inhibiting K-Hcy by targeting MARS reversed these effects and suppressed oncogenic CRC cell growth. Our study reveals a mechanism of Western-diet-associated CRC and highlights an intervention approach for reversing diet-induced oncogenic effects. : Wang et al. find that high-fat diet induces K-Hcy through elevating colonic MARS expression. They show that K-Hcy modification of ATR suppresses DNA damage repair to result in an accumulation of colonic DNA damage. Keywords: high-fat diet, lysine homocysteinylation, DNA damage repair, colorectal cancer, ataxia-telangiectasia and Rad3-related protein
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- 2018
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5. Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake
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Hu, Song-Hua, primary, He, Xia-Di, additional, Nie, Ji, additional, Hou, Jun-Li, additional, Wu, Jiang, additional, Liu, Xiao-Yan, additional, Wei, Yun, additional, Tang, Hui-Ru, additional, Sun, Wen-Xing, additional, Zhou, Shu-Xian, additional, Yuan, Yi-Yuan, additional, An, Yan-Peng, additional, Yan, Guo-Quan, additional, Lin, Yan, additional, Lin, Peng-Cheng, additional, Zhao, Jean J., additional, Ye, Ming-Liang, additional, Zhao, Jian-Yuan, additional, Xu, Wei, additional, and Zhao, Shi-Min, additional
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- 2022
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6. Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation
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Zhang, Xuan, primary, Qu, Yuan-Yuan, additional, Liu, Lian, additional, Qiao, Ya-Nan, additional, Geng, Hao-Ran, additional, Lin, Yan, additional, Xu, Wei, additional, Cao, Jing, additional, and Zhao, Jian-Yuan, additional
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- 2021
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7. Homocysteine inhibits pro-insulin receptor cleavage and causes insulin resistance via protein cysteine-homocysteinylation
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Lian Liu, Jian-Yuan Zhao, Ya-Nan Qiao, Wei Xu, Hao-Ran Geng, Jing Cao, Yuan-Yuan Qu, Xuan Zhang, and Yan Lin
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Male ,Hyperhomocysteinemia ,CHO Cells ,General Biochemistry, Genetics and Molecular Biology ,symbols.namesake ,Insulin resistance ,Cricetulus ,Antigens, CD ,medicine ,Animals ,Humans ,Receptor ,Protein disulfide-isomerase ,Muscle, Skeletal ,Furin ,Homocysteine ,Proinsulin ,biology ,Chemistry ,Endoplasmic reticulum ,Hep G2 Cells ,Golgi apparatus ,medicine.disease ,Receptor, Insulin ,Cell biology ,Rats ,Mice, Inbred C57BL ,Insulin receptor ,Disease Models, Animal ,HEK293 Cells ,Adipose Tissue ,Diabetes Mellitus, Type 2 ,Liver ,symbols ,biology.protein ,Insulin Resistance ,Protein Processing, Post-Translational ,Cysteine - Abstract
Summary Elevation in homocysteine (Hcy) level is associated with insulin resistance; however, the causality between them and the underlying mechanism remain elusive. Here, we show that Hcy induces insulin resistance and causes diabetic phenotypes by protein cysteine-homocysteinylation (C-Hcy) of the pro-insulin receptor (pro-IR). Mechanistically, Hcy reacts and modifies cysteine-825 of pro-IR in the endoplasmic reticulum (ER) and abrogates the formation of the original disulfide bond. C-Hcy impairs the interaction between pro-IR and the Furin protease in the Golgi apparatus, thereby hindering the cleavage of pro-IR. In mice, an increase in Hcy level decreases the mature IR level in various tissues, thereby inducing insulin resistance and the type 2 diabetes phenotype. Furthermore, inhibition of C-Hcy in vivo and in vitro by overexpressing protein disulfide isomerase rescues the Hcy-induced phenotypes. In conclusion, C-Hcy in the ER can serve as a potential pharmacological target for developing drugs to prevent insulin resistance and increase insulin sensitivity.
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- 2021
8. Methylene-bridge tryptophan fatty acylation regulates PI3K-AKT signaling and glucose uptake
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Song-Hua Hu, Xia-Di He, Ji Nie, Jun-Li Hou, Jiang Wu, Xiao-Yan Liu, Yun Wei, Hui-Ru Tang, Wen-Xing Sun, Shu-Xian Zhou, Yi-Yuan Yuan, Yan-Peng An, Guo-Quan Yan, Yan Lin, Peng-Cheng Lin, Jean J. Zhao, Ming-Liang Ye, Jian-Yuan Zhao, Wei Xu, and Shi-Min Zhao
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Mice ,Phosphatidylinositol 3-Kinases ,Glucose ,Docosahexaenoic Acids ,Eicosapentaenoic Acid ,Acylation ,Fatty Acids, Unsaturated ,Tryptophan ,Animals ,Proto-Oncogene Proteins c-akt ,General Biochemistry, Genetics and Molecular Biology ,Article ,Signal Transduction - Abstract
Protein fatty acylation regulates numerous cell signaling pathways. Polyunsaturated fatty acids (PUFAs) exert a plethora of physiological effects, including cell signaling regulation, with underlying mechanisms to be fully understood. Herein, we report that docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) regulate PI3K-AKT signaling by modifying PDK1 and AKT2. DHA-administered mice exhibit altered phosphorylation of proteins in signaling pathways. Methylene bridge-containing DHA/EPA acylate δ1 carbon of tryptophan 448/543 in PDK1 and tryptophan 414 in AKT2 via free radical pathway, recruit both the proteins to the cytoplasmic membrane, and activate PI3K signaling and glucose uptake in a tryptophan acylation-dependent but insulin-independent manner in cultured cells and in mice. DHA/EPA deplete cytosolic PDK1 and AKT2 and induce insulin resistance. Akt2 knockout in mice abrogates DHA/EPA-induced PI3K-AKT signaling. Our results identify PUFA’s methylene bridge tryptophan acylation, a protein fatty acylation that regulates cell signaling and may underlie multifaceted effects of methylene-bridge-containing PUFAs.
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- 2021
9. Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair
- Author
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Jian-Yuan Zhao, Wei Xu, Yuan-Yuan Qu, Yan Lin, Xinyu Mei, Rui Zhao, Xuan Zhang, Yiming Chen, Chao Chen, Zhi-Gui Zuo, Shao-Bo Yang, Shimin Zhao, Qian Zhou, Yang Li, and Dan Wang
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0301 basic medicine ,Male ,DNA Repair ,DNA damage ,Colorectal cancer ,Cell ,Lysine ,Apoptosis ,Diet, High-Fat ,General Biochemistry, Genetics and Molecular Biology ,03 medical and health sciences ,chemistry.chemical_compound ,Mice ,0302 clinical medicine ,medicine ,Tumor Cells, Cultured ,Animals ,Humans ,Rats, Wistar ,lcsh:QH301-705.5 ,Homocysteine ,Cell Proliferation ,Mice, Inbred BALB C ,Mice, Inbred ICR ,Chemistry ,Effector ,Rectal Neoplasms ,medicine.disease ,Phenotype ,Xenograft Model Antitumor Assays ,digestive system diseases ,Rats ,030104 developmental biology ,medicine.anatomical_structure ,lcsh:Biology (General) ,030220 oncology & carcinogenesis ,Case-Control Studies ,Colonic Neoplasms ,Cancer research ,Protein Processing, Post-Translational ,DNA ,DNA Damage ,Signal Transduction - Abstract
Summary: Colorectal cancer (CRC) onset is profoundly affected by Western diet. Here, we report that high-fat (HF) diet-induced, organ-specific colonic lysine homocysteinylation (K-Hcy) increase might promote CRC onset by impeding DNA damage repair. HF chow induced elevated methionyl-tRNA synthetase (MARS) expression and K-Hcy levels and DNA damage accumulation in the mouse and rat colon, resulting in a phenotype identical to that of CRC tissues. Moreover, the increased copy number of MARS, whose protein product promotes K-Hcy, correlated with increased CRC risk in humans. Mechanistically, MARS preferentially bound to and modified ataxia-telangiectasia and Rad3-related protein (ATR), inhibited ATR and its downstream effectors checkpoint kinase-1 and p53, and relieved cell-cycle arrest and decreased DNA damage-induced apoptosis by disrupting the binding of ATR-interacting protein to ATR. Inhibiting K-Hcy by targeting MARS reversed these effects and suppressed oncogenic CRC cell growth. Our study reveals a mechanism of Western-diet-associated CRC and highlights an intervention approach for reversing diet-induced oncogenic effects. : Wang et al. find that high-fat diet induces K-Hcy through elevating colonic MARS expression. They show that K-Hcy modification of ATR suppresses DNA damage repair to result in an accumulation of colonic DNA damage. Keywords: high-fat diet, lysine homocysteinylation, DNA damage repair, colorectal cancer, ataxia-telangiectasia and Rad3-related protein
- Published
- 2018
10. Colonic Lysine Homocysteinylation Induced by High-Fat Diet Suppresses DNA Damage Repair
- Author
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Wang, Dan, primary, Zhao, Rui, additional, Qu, Yuan-Yuan, additional, Mei, Xin-Yu, additional, Zhang, Xuan, additional, Zhou, Qian, additional, Li, Yang, additional, Yang, Shao-Bo, additional, Zuo, Zhi-Gui, additional, Chen, Yi-Ming, additional, Lin, Yan, additional, Xu, Wei, additional, Chen, Chao, additional, Zhao, Shi-Min, additional, and Zhao, Jian-Yuan, additional
- Published
- 2018
- Full Text
- View/download PDF
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