Endoplasmic reticulum stress eIF2α-ATF4 pathway-mediated cyclooxygenase-2 induction regulates cadmium-induced autophagy in kidney.

ABSTRACT: The heavy metal cadmium (Cd) is nephrotoxic. Recent studies show that autophagy plays an essential role in Cd-induced kidney injury. However, the mechanisms of Cd-induced kidney injury accompanied by autophagy are still obscure. In the present study, we first confirmed that Cd induced kidney damage and dysfunction, along with autophagy, both in vivo and in vitro. Then, we observed that cyclooxygenase-2 (COX-2) and the eIF2α-ATF4 pathway of endoplasmic reticulum (ER) stress were induced by Cd in both kidney tissues and cultured cells. Further studies showed that inhibition of COX-2 with celecoxib or RNA interference (RNAi) inhibited the Cd-induced autophagy in kidney cells. In addition, blocking ER stress with 4-phenylbutyrate or RNAi partially counteracted COX-2 overexpression and autophag

SUBMITTER: Luo B 

PROVIDER: S-EPMC5143407 | biostudies-literature | 2016 Jun

REPOSITORIES: biostudies-literature