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Cyclosporin A aggravates hydrogen peroxide-induced cell death in kidney proximal tubule epithelial cells / 대한해부학회지
Anatomy & Cell Biology ; : 312-323, 2019.
Article in English | WPRIM | ID: wpr-762231
ABSTRACT
Cyclosporin A (CsA) does not only exert a toxic effect on kidney parenchymal cells, but also protects them against necrotic cell death by inhibiting opening of mitochondrial permeability transition pore. However, whether CsA plays a role in hydrogen peroxide-induced kidney proximal tubular cell death is currently unclear. In the present study, treatment with CsA further increased apoptosis and necrosis in HK-2 human kidney proximal tubule epithelial cells during exposure to hydrogen peroxide. In addition, hydrogen peroxide-induced p53 activation and BH3 interacting-domain death agonist (BID) expression were higher in CsA-treated cells than those in non-treated cells, whereas hydrogen peroxide-induced activation of mitogen-activated protein kinases including p38, c-Jun N-terminal kinase, and extracellular signal-regulated kinase and activation of protein kinase B were not significantly altered by treatment with CsA. In oxidant-antioxidant system, reactive oxygen species (ROS) production induced by hydrogen peroxide was further enhanced by treatment with CsA. However, expression levels of antioxidant enzymes including manganese superoxide dismutase, copper/zinc superoxide dismutase, and catalase were not altered by treatment with hydrogen peroxide or CsA. Treatment with CsA further enhanced mitochondrial membrane potential induced by exposure to hydrogen peroxide, although it did not alter endoplasmic reticulum stress based on expression of glucose-regulated protein 78 and 94. Taken together, these data suggest that CsA can aggravate hydrogen peroxide-induced cell death through p53 activation, BID expression, and ROS production.
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Full text: Available Index: WPRIM (Western Pacific) Main subject: Permeability / Phosphotransferases / Superoxide Dismutase / Catalase / Cyclosporine / Cell Death / Reactive Oxygen Species / Apoptosis / Mitogen-Activated Protein Kinases / JNK Mitogen-Activated Protein Kinases Limits: Humans Language: English Journal: Anatomy & Cell Biology Year: 2019 Type: Article

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Full text: Available Index: WPRIM (Western Pacific) Main subject: Permeability / Phosphotransferases / Superoxide Dismutase / Catalase / Cyclosporine / Cell Death / Reactive Oxygen Species / Apoptosis / Mitogen-Activated Protein Kinases / JNK Mitogen-Activated Protein Kinases Limits: Humans Language: English Journal: Anatomy & Cell Biology Year: 2019 Type: Article