Role of subcellular calcium redistribution in regulating apoptosis and autophagy in cadmium-exposed primary rat proximal tubular cells.

Role of subcellular calcium redistribution in regulating apoptosis and autophagy in cadmium-exposed primary rat proximal tubular cells. J Inorg Biochem. 2016 Sep 14; Authors: Liu F, Li ZF, Wang ZY, Wang L Abstract Ca(2+) signaling plays a vital role in regulating apoptosis and autophagy. We previously proved that cytosolic Ca(2+) overload is involved in cadmium (Cd)-induced apoptosis in rat proximal tubular (rPT) cells, but the source of elevated cytosolic Ca(2+) concentration ([Ca(2+)]c) and the effect of potential subcellular Ca(2+) redistribution on apoptosis and autophagy remain to be elucidated. Firstly, data showed that Cd-induced elevation of [Ca(2+)]c was primarily generated intracellularly. Moreover, elevations of [Ca(2+)]c and mitochondrial Ca(2+) concentration ([Ca(2+)]mit) with depletion of endoplasmic reticulum (ER) Ca(2+) levels ([Ca(2+)]ER) were revealed in Cd-treated rPT cells, but this subcellular Ca(2+) redistribution was significantly suppressed by 2-Aminoethoxydiphenyl borate (2-APB). Elevated inositol 1,4,5-trisphosphate (IP3) levels with up-regulated IP3 receptor (IP3R) protein levels were shown in Cd-exposed cells, confirming that IP3R-mediated ER Ca(2+) release results in the elevation of [Ca(2+)]c. Up-regulated sequestosome 1 (p62) protein levels and autophagic flux assay demonstrated that Cd impaired autophagic degradation, while N-acetylcysteine (NAC) markedly attenuated Cd-induced p62 and microtubule-assoc...
Source: Journal of Inorganic Biochemistry - Category: Biochemistry Authors: Tags: J Inorg Biochem Source Type: research