Overexpression and Low Expression of Selenoprotein S Impact Ochratoxin A-Induced Porcine Cytotoxicity and Apoptosis in Vitro.

Abstract

Our previous study demonstrated that selenium could alleviate ochratoxin A (OTA)-induced nephrotoxicity in PK15 cells. Selenoprotein S (SelS) has antioxidant activities, but it is unclear whether SelS plays a role in the alleviating effects of selenium on OTA-induced nephrotoxicity. We previously have stably transfected pig pCDNA3.1-SelS to PK15 cells to overexpress SelS. Here, we demonstrated that SelS overexpression alleviated OTA-induced cytotoxicity and apoptosis as demonstrated by cell viabilities, LDH activities, Annexin V-bing, caspase 3 activities, and apoptotic nuclei. SelS overexpression increased glutathione (GSH) levels and decreased reactive oxygen species (ROS) and malondialdehyde levels in PK15 cells, regardless of OTA treatment. SelS overexpression inhibited OTA-induced p38 phosphorylation. Adding buthionine sulfoximine reversed all of the above SelS-induced changes. In addition, the knockdown of SelS by SelS-specific siRNA decreased GSH levels, increased ROS levels, and aggravated OTA-induced p38 phosphorylation. The knockdown of SelS aggravated OTA-induced cytotoxicity and apoptosis in PK15 cells. These data indicate that pig SelS overexpression and lowexpression impact OTA-induced cytotoxicity and apoptosis by modulating the oxidative stress and p38 phosphorylation. Our work provides new insights into the relationship between SelS- and OTA-induced cytotoxicity and apoptosis and describes an antitoxic mechanism of action for Se.