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Dissection of Targeting Molecular Mechanisms of Aristolochic Acid-induced Nephrotoxicity via a Combined Deconvolution Strategy of Chemoproteomics and Metabolomics.

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收录情况： ◇ SCIE

作者：
Zhang Qian[1,2,3] * ; Luo Piao[1,3] * ; Chen Jiayun[1] * ; Yang Chuanbin[4] * ; Xia Fei[1] ; Zhang Junzhe[1] ; Tang Huan[1] ; Liu Dandan[1] ; Gu Liwei[1] ; Shi Qiaoli[1] ; He Xueling[1] ; Yang Tong[1] ; Wang Jigang[1,2,3,4,5,6,7] ;
机构： [1]Artemisinin research center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. [2]School of Chinese Materia Medica, and State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. [3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. [4]Department of Urology, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong 518020, China. [5]Center for Reproductive Medicine, Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan 523125, China. [6]Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524037, China. [7]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
出处：
DOI： 10.7150/ijbs.69618
ISSN：

关键词： Aristolochic acid nephropathy chemical proteomics mitochondrial dysfunction apoptosis metabolism

摘要：
Aristolochic acid (AA), mainly derived from herbal Aristolochia and Asarum plants, was listed as a human carcinogen class I in 2002. Aristolochic acid nephropathy (AAN) is a rapidly progressive tubulointerstitial nephritis and urothelial cancer caused by AA. However, the targeting molecular mechanisms of AAs-induced nephrotoxicity are largely unclear. This study aims to dissect targeting molecular mechanisms of AA-induced nephrotoxicity. Activity-based protein profiling (ABPP) in combination with cellular thermal shift assay (CETSA) was performed to identify the AAs binding target proteins. Our data indicated that several key enzymes in the metabolic process and mitochondrial respiration including IDH2 and MDH2 (Krebs cycle), PKM and LDH (aerobic respiration), FASN (fatty acid beta-oxidation), HK2 (glucose metabolism), and ATP synthase were identified as directly binding targets of AAs. Metabolomics and oxygen consumption rate (OCR) experiments further confirmed that AAs targeting proteins disrupted metabolic biosynthesis processes and impaired mitochondrial functions. Ultimately, AAs induced renal cells apoptosis by disturbing various biological processes. Cumulatively, AAs may directly bind to key proteins involved in the metabolic process and mitochondrial homeostasis, and finally induce aristolochic acid nephropathy. Our findings provide novel insight into underlying mechanisms of AAs-induced kidney toxicity, which may help to develop therapeutic strategies for AAN.© The author(s).

基金：
National Key Research and Development Program of China (2020YFA0908000); the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (No: ZYYCXTD-C-202002); the National Natural Science Foundation of China (82074098 and 81903588); the CACMS Innovation Fund (CI2021A05101); the Fundamental Research Funds for the Central public welfare research institutes (ZZ14- YQ-050, ZZ14-YQ-051, ZZ14-ND-010, ZZ15-ND-10, ZZ14-FL-002 and ZZ15-YQ-063).
语种：
外文
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PubmedID：
中科院(CAS)分区：
出版当年[2021]版：
大类 | 2 区 生物学
小类 | 2 区 生化与分子生物学
最新[2025]版：
大类 | 1 区 生物学
小类 | 2 区 生化与分子生物学
JCR分区：
出版当年[2020]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
最新[2023]版：
Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

影响因子： 最新[2023版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

第一作者：
第一作者机构： [1]Artemisinin research center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. [2]School of Chinese Materia Medica, and State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. [3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China.
共同第一作者：
通讯作者：
通讯机构： [1]Artemisinin research center, and Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing 100700, China. [2]School of Chinese Materia Medica, and State Key Laboratory of Component-based Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin 301617, China. [3]School of Traditional Chinese Medicine, Southern Medical University, Guangzhou 510515, China. [4]Department of Urology, The Second Clinical Medical College, Jinan University (Shenzhen People’s Hospital), Shenzhen, Guangdong 518020, China. [5]Center for Reproductive Medicine, Dongguan Maternal and Child Health Care Hospital, Southern Medical University, Dongguan 523125, China. [6]Central People's Hospital of Zhanjiang, Zhanjiang, Guangdong 524037, China. [7]Guangdong Provincial Key Laboratory of New Drug Screening, School of Pharmaceutical Sciences, Southern Medical University, Guangzhou 510515, China.
推荐引用方式(GB/T 7714)：
Zhang Qian,Luo Piao,Chen Jiayun,et al.Dissection of Targeting Molecular Mechanisms of Aristolochic Acid-induced Nephrotoxicity via a Combined Deconvolution Strategy of Chemoproteomics and Metabolomics.[J].INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES.2022,18(5):2003-2017.doi:10.7150/ijbs.69618.
APA：
Zhang Qian,Luo Piao,Chen Jiayun,Yang Chuanbin,Xia Fei...&Wang Jigang.(2022).Dissection of Targeting Molecular Mechanisms of Aristolochic Acid-induced Nephrotoxicity via a Combined Deconvolution Strategy of Chemoproteomics and Metabolomics..INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES,18,(5)
MLA：
Zhang Qian,et al."Dissection of Targeting Molecular Mechanisms of Aristolochic Acid-induced Nephrotoxicity via a Combined Deconvolution Strategy of Chemoproteomics and Metabolomics.".INTERNATIONAL JOURNAL OF BIOLOGICAL SCIENCES 18..5(2022):2003-2017

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