Endoplasmic reticulum-mitochondria coupling attenuates vanadium-induced apoptosis via IP3R in duck renal tubular epithelial cells

Vanadium (V) is necessary for the health and growth of Animals, but excessive V has harmful effects on the ecosystem health. Endoplasmic reticulum (ER)-mitochondria coupling as a membrane structure connects the mitochondrial outer membrane with the ER. The mitochondria-associated ER membrane (MAM) is a region of the ER-mitochondria coupling and is essential for normal cell function. Currently, the crosstalk between ER-mitochondrial coupling and Apoptosis in the toxic mechanism of V on duck kidney is still unclear. In this study, duck renal tubular epithelial cells were incubated with different concentrations of sodium metavanadate (NaVO₃) and/or inositol triphosphate receptor (IP₃R) inhibitor 2-aminoethyl diphenyl borate (2-APB) for 24 h. The results showed that V could significantly increase Lactate Dehydrogenase (LDH) release, the mitochondrial calcium level and the numbers of the fluorescent signal points of IP₃R; shortened the length ER-mitochondria coupling and reduced its formation; markedly upregulate the mRNA levels of MAM-related genes and protein levels, causing MAM dysfunction. Additionally, V treatment appeared to upregulate pro-apoptotic genes and downregulate anti-apoptotic genes, followed by cell Apoptosis. The V-induced changes were alleviated by treatment with IP₃R inhibitor. In summary, V could induce the dysfunction of ER-mitochondrial coupling and Apoptosis, and inhibition of ER-mitochondrial coupling could attenuate V-induced Apoptosis in duck renal tubular epithelial cells.