title: Protective effects of andrographolide analogue AL-1 on ROS-induced RIN-mβ cell death by inducing ROS generation.
abstract: Oxidative stress is considered to be a major factor contributing to pathogenesis and progression of many diseases. A novel andrographolide-lipoic acid conjugate (AL-1) could protect pancreatic β-cells from reactive oxygen species (ROS)-induced oxidative injury. However, its protective mechanism is still unclear. In this work, we used proteomics to identify AL-1-regulated proteins in β-cells and found that 13 of the 71 proteins regulated by AL-1 were closely associated with antioxidation. These differential proteins were mainly involved in the ERK1/2 and AKT1 signaling pathways. Functional investigation demonstrated that AL-1 exerted its protective effects on H2O2-induced cell death of β-cells by generating NADPH oxidase-dependent ROS to activate ERK1/2 and AKT1 signaling pathways. As a consequence, the expressions of antioxidant proteins including Trx1, Prx1 and Prx5, and anti-apoptotic proteins including PDCD6IP, prohibitin, galectin-1 and HSP were upregulated. AL-1 probably worked as a "vaccinum" to activate the cellular antioxidant system by inducing the generation of low concentration ROS which then reciprocally protected β-cells from oxidative damage caused by high-level ROS from H2O2. To the best of our knowledge, this is the first comprehensive proteomic analysis illustrating a novel molecular mechanism for the protective effects of antioxidants on β-cells from H2O2-induced cell death.
authors.affiliation: Key Laboratory of Functional Protein Research of Guangdong Higher Education Institutes, Institute of Life and Health Engineering, College of Life Science and Technology, Jinan University, Guangzhou, China. tgryan@jnu.edu.cn
authors.forename: Guang-Rong
authors.initials: GR
authors.lastname: Yan
authors.forename: Hui-Hua
authors.initials: HH
authors.lastname: Zhou
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Yin
authors.initials: Y
authors.lastname: Zhong
authors.forename: Zi-Lu
authors.initials: ZL
authors.lastname: Tan
authors.forename: Yuqiang
authors.initials: Y
authors.lastname: Wang
authors.forename: Qing-Yu
authors.initials: QY
authors.lastname: He
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D019610:Cytoprotection / Q000187:drug effects*; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D050417:Insulin-Secreting Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D019255:NADPH Oxidases / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects; D060066:Protein Interaction Maps / Q000187:drug effects; D040901:Proteomics; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism*; D008063:Thioctic Acid / Q000737:chemistry*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D004224:Diterpenes; D017382:Reactive Oxygen Species; C030419:andrographolide; D008063:Thioctic Acid; D006861:Hydrogen Peroxide; D019255:NADPH Oxidases