title: The inhibitory effect of angiotensin II on BKCa channels in podocytes via oxidative stress.
abstract: Angiotensin II (Ang II) is an important active substance of the renin-angiotensin system (RAS). The present study has confirmed that abnormalities of Ang II may be related with cerebrovascular diseases, endocrine diseases, cardiovascular diseases, liver diseases, such as: cerebral hypoxia, diabetes, obesity, atrial fibrillation, and liver cirrhosis. However, understanding effects of Ang II on podocytes is not enough. This study was to investigate the effects of oxidative stress on the large conductance, Ca(2+)-activated K(+) channels (BKCa). Results from the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay showed that Ang II induced podocyte death in a concentration-dependent manner. The measurement of superoxide dismutase (SOD) generation demonstrated that Ang II decreased the total SOD of cellular levels. Meaningfully, pretreatment of a type of ROS scavenger formulations named N-(mercaptopropionyl)-glycine (N-MPG) could inhibit podocyte apoptosis induced by Ang II. Meanwhile, patch-clamp technique was used in this study to detect the effects of Ang II on currents of BKCa channel in podocytes. The results indicated that Ang II inhibited the current amplitude of BKCa channel and decreased the slope of I-V curve. Ang II also made the activation curves of BKCa channel shift to the left. These results may provide a theoretical basis for potential treatment of chronic glomerular disease in the future.
authors.affiliation: School of Medicine, State Key Laboratory of Medicinal Chemical Biology, Tianjin Key Laboratory of Tumor Microenvironment and Neurovascular Regulation, Nankai University, Tianjin, 300071, China.
authors.forename: Na
authors.initials: N
authors.lastname: Gao
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaochen
authors.initials: X
authors.lastname: Zhang
authors.forename: Zhuo
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015640:Ion Channel Gating / Q000187:drug effects*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D051379:Mice; D018384:Oxidative Stress / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D050199:Podocytes / Q000187:drug effects* / Q000378:metabolism / Q000502:physiology; D013482:Superoxide Dismutase / Q000378:metabolism
chemical_list: C530995:BKCa protein, mouse; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D000804:Angiotensin II; D013482:Superoxide Dismutase