Premium
Calcium Uptake via Mitochondrial Uniporter Contributes to Palmitic Acid‐Induced Apoptosis in Mouse Podocytes
Author(s) -
Yuan Zeting,
Cao Aili,
Liu Hua,
Guo Hengjiang,
Zang Yingjun,
Wang Yi,
Wang Yunman,
Wang Hao,
Yin Peihao,
Peng Wen
Publication year - 2017
Publication title -
journal of cellular biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.028
H-Index - 165
eISSN - 1097-4644
pISSN - 0730-2312
DOI - 10.1002/jcb.25930
Subject(s) - uniporter , microbiology and biotechnology , palmitic acid , apoptosis , ruthenium red , thapsigargin , ryanodine receptor , cytochrome c , chemistry , mitochondrion , cytosol , calcium , biochemistry , biology , endoplasmic reticulum , fatty acid , organic chemistry , enzyme
ABSTRACT Podocytes are component cells of the glomerular filtration barrier, and their loss by apoptosis is the main cause of proteinuria that leads to diabetic nephropathy (DN). Therefore, insights into podocyte apoptosis mechanism would allow a better understanding of DN pathogenesis and thus help develop adequate therapeutic strategies. Here, we investigated the molecular mechanism of palmitic acid‐inhibited cell death in mouse podocytes, and found that palmitic acid increased cell death in a dose‐ and time‐dependent manner. Palmitic acid induces apoptosis in podocytes through upregulation of cytosolic and mitochondrial Ca 2+ , mitochondrial membrane potential (MMP), cytochrome c release, and depletion of endoplasmic reticulum (ER) Ca 2+ . The intracellular calcium chelator, 1,2‐bis (2‐aminophenoxy) ethane‐ N , N , N , N ′‐tetraacetic acid tetrakis acetoxymethyl ester (BAPTA‐AM), partially prevented this upregulation whereas 2‐aminoethoxydiphenyl borate (2‐APB), an inositol 1,4,5‐triphosphate receptor (IP3R) inhibitor; dantrolene, a ryanodine receptor (RyR) inhibitor; and 4,4′‐diisothiocyanatostibene‐2,2′‐disulfonic acid (DIDS), an anion exchange inhibitor, had no effect. Interestingly, ruthenium red and Ru360, both inhibitors of the mitochondrial Ca 2+ uniporter (MCU), blocked palmitic acid‐induced mitochondrial Ca 2+ elevation, cytochrome c release from mitochondria to cytosol, and apoptosis. siRNA to MCU markedly reduced palmitic acid‐induced apoptosis. These data indicate that Ca 2+ uptake via mitochondrial uniporter contributes to palmitic acid‐induced apoptosis in mouse podocytes. J. Cell. Biochem. 118: 2809–2818, 2017. © 2017 Wiley Periodicals, Inc.