Author:
Zang Yingjun,Liu Shuang,Cao Aili,Shan Xiangyu,Deng Wenjuan,Li Zhijun,Wang Hao,Wang Yunman,Wang Li,Peng Wen
Abstract
AbstractLoss of podocytes is a hallmark of diabetic nephropathy, and a growing body of evidence indicates that podocytes are susceptible to palmitic acid (PA). We have previously shown that AS-IV inhibited PA-induced podocyte apoptosis by activating sarcoendoplasmic reticulum Ca2+ ATPase (SERCA), which indicate calcium regulation may involve in the process. Immunofluorescence staining, Western blot and flow cytometry were used to measure the protective efficacy of AS-IV to ameliorate PA-induced ER stress and podocyte apoptosis. Meanwhile, AS-IV inhibited cytochrome c release, decreased mitochondrial membrane potential, accompany with the depletion of endoplasmic reticulum Ca2+ and elevation of cytosolic and mitochondrial Ca2+. Sequestration of cytosolic calcium with BAPTA-AM limited the response of podocyte apoptosis, while during the process the effect of AS-IV was also restrained. In contrast, elevation of cytosolic calcium with calcium ionophore ionomycin was depressed by AS-IV addition. Furthermore, inhibiting TRPC6 expression with SKF96365 or TRPC6 siRNA counteracted the beneficial effect of AS-IV. Our study provides further evidence to conclude the inhibitory effect of AS-IV to podocyte apoptosis is Ca2+-dependent. And the efficacy correlates with inhibiting TRPC6-mediated Ca2+ influx, and then cellular Ca2+ disturbance was coordinated.
Funder
National Natural Science Foundation of China
Exploration Program of Putuo Hospital
Key Medical Discipline Project of Shanghai Municipal Health Bureau
Youth project of Shanghai Municipal Commission of Health and Family Planning
Planned Science Program of the Shanghai University of Traditional Chinese Medicine
Science and Technology Innovation Project of Putuo District Health System
Publisher
Springer Science and Business Media LLC
Subject
Genetics,Molecular Biology,General Medicine
Cited by
10 articles.
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