IP3R-Grp75-VDAC1-MCU calcium regulation axis antagonists protect podocytes from apoptosis and decrease proteinuria in an Adriamycin nephropathy rat model

• DOI: 10.1186/s12882-018-0940-3
• Publication Date: 2018-06-15T00:17:50Z
• Authors: Han Xu; Na Guan; Ya-Li Ren; Qi-Jiao Wei; Ying-Hong Tao; Guo-Sheng Yang; Xiao-Ya Liu; Ding-Fang Bu; Ying Zhang; Sai-Nan Zhu
• Keywords: Nephrology

The mechanism of podocyte apoptosis is not fully understood. In addition, the role inositol 1,4,5-triphosphate receptor (IP3R)/glucose-regulated protein 75 (Grp75)/voltage-dependent anion channel 1 (VDAC1)/mitochondrial calcium uniporter (MCU) regulation axis, which located at sites endoplasmic reticulum (ER) mitochondria coupling, in unclear. This study aimed to understand roles this axis and explore potential targets for protection. expression IP3R, Grp75, VDAC1, MCU mitochondrial Ca2+ were analyzed during Adriamycin- or angiotensin II-induced cultured mouse podocytes. interaction between VDAC1 was investigated using co-immunoprecipitation experiments. effects agonists antagonists on podocyte-protective an inhibitor further rats with Adriamycin-induced nephropathy. Increased MCU, enhanced among IP3R-Grp75-VDAC1 complex, overload, increased active caspase-3 levels confirmed apoptosis. Agonists facilitated overload apoptosis, whereas specific against prevented A proteinuria foot process effacement rats. identified a novel pathway IP3R-Grp75-VDAC1-MCU mediated by facilitating overload. Antagonists that inhibit transfer from ER protected podocytes An decreased Therefore, have promise as drugs.