Abstract
The potential antagonistic mechanism between zinc (Zn) and arsenic (As) on renal toxicity was investigated in common carp. The results showed that by increased Zn efflux and retention (as reflected by zinc transporter 1 (ZnT-1), Zrt- and Irt- 1ike protein (ZIP) and metallothionein (MT) expression), Zn co-administration significantly recovered the antioxidant function (catalase, CAT) and the level of renal barrier function (Occludin, Claudins and Zonula Occludens) in comparison to As treatment. Interestingly, Zn co-administration with As resulted in carps undergoing reduction of heat shock response (HSPs), a low induction of autophagy flux (Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) and sequestosome 1 (P62)) and decreased endoplasmic reticulum (ER) stress (activating transcription factor 6 (ATF-6), inositol requiring-1α (IRE1) and PKR-like ER kinase (PERK)) in the aspect of mRNA or protein levels. All these alleviated protein quality control processes induced by Zn under As stress was correlated with the no longer loosen tight connection, less swollen endoplasmic reticulum as well as reduced formation of autophagosomes and autophagic vesicles. Mechanically, post-transcriptional regulated protein quantities compromising phosphatidylinositol-3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway was demonstrated true causative forces inside the cell for Zn against As poisoning. In conclusion, we suggested the potential renal protective effect of Zn supplementation against As exposure by the modulation of protein quality control processes.