Andrographolide sodium bisulfate-induced apoptosis and autophagy in human proximal tubular endothelial cells is a ROS-mediated pathway |
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| Affiliation: | 1. School of Pharmacology, Zhejiang Chinese Medical University, Hangzhou 310053, Zhejiang Province, China;2. Institute of Materia Medica, Zhejiang Academy of Medical Sciences, Hangzhou 310013, Zhejiang Province, China;1. Department of Biochemistry and Biotechnology, Precarpathian National University named after Vassyl Stefanyk, 57 Shevchenko Str., Ivano-Frankivsk 76025, Ukraine;2. Institute of Biochemistry, Carleton University, 1125 Colonel By Drive, Ottawa, Ontario K1S 5B6, Canada;1. Radiation Biotechnology Laboratory, Department of Radiation Biosciences, Institute of Nuclear and Allied Sciences, Delhi 110054, India;2. Department of Biochemistry, Faculty of Science, Jamia Hamdard, Delhi 110062, India;1. Department of Chemical and Biological Engineering, Yancheng Institute of Technology, Yancheng 224003, PR China;2. State Key Laboratory of Pollution Control and Resources Reuse, School of Environment, Nanjing University, Nanjing 210046, Jiangsu, PR China;1. ILDONG Research Laboratories, ILDONG Pharmaceutical Co. Ltd., Hwaseong, Gyeonggi 445-710, Republic of Korea;2. College of Pharmacy, Chungbuk National University, Cheongju 361-763, Republic of Korea;3. Department of Biological Sciences, Konkuk University, 1 Hwayang-dong, Gwangjin-gu, Seoul 143-701, Republic of Korea |
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| Abstract: | Background and aimsThe nephrotoxic mechanisms of andrographolide sodium bisulfate (ASB) remain largely unknown. This study attempted to explore the mechanism of ASB-induced nephrotoxicity using human proximal tubular endothelial cells (HK-2).MethodsFor this study HK-2 cells were treated with rising concentrations of ASB. Their survival rate was detected using MTT assay and ultrastructure was observed with electron microscopy. l-Lactate dehydrogenase (LDH) assay was followed by examination of mitochondrial membrane potential (MMP). Reactive oxygen species (ROS) was detected using different methods and apoptosis/autophage related proteins were detected using immunoblotting.ResultsWe found that ASB inhibited HK-2 cell proliferation and decreased cell survival rate in a time and dose-dependent manner (P < 0.05, P < 0.01, respectively). With increasing ASB concentration, cell structure was variably damaged and evidence of apoptosis and autophagy were observed. MMP gradually decreased and ROS was induced. The expression of JNK and Beclin-1 increased and activation of the JNK signaling pathway were seen. Apoptosis was induced via the mitochondrial-dependent caspase-3 and caspase-9 pathway, and autophagy related protein Beclin-1 was enhanced by ASB.ConclusionThe data show that ASB induces high levels of ROS generation in HK-2 cells and activates JNK signaling. Furthermore, ASB induces cell apoptosis via the caspase-dependent mitochondrial pathway, and induces cellular autophagy, in part by enhancing Beclin-1 protein expression. |
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| Keywords: | Andrographolide sodium bisulfate Human proximal tubular endothelial cell Reactive oxygen species Apoptosis Autophagy |
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