Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells. (March 2021)

• Record Type: Journal Article
• Authors: Hou, Lili; Yuan, Xin; Le, Guannan; Lin, Ziman; Gan, Fang; Li, Haolei; Huang, Kehe
• Is Part Of: Food and chemical toxicology. Volume 149(2021)
• Publication Date: 2021-03
• Subjects: Fumonisin B1 -- Nephrotoxicity -- Oxidative stress -- mTORC1 -- Autophagy -- HK-2 cells; Toxicology -- Periodicals; Food poisoning -- Periodicals; Food Poisoning -- Periodicals; Toxicology -- Periodicals; Toxicologie -- Périodiques; Intoxications alimentaires -- Périodiques; Food poisoning; Toxicology; Periodicals; Electronic journals; 615.9
• DOI: 10.1016/j.fct.2021.112037
• Languages: English
• ISSNs: 0278-6915

Abstract

Abstract: Fumonisin B1 (FB1), a worldwide contaminating mycotoxin, can cause global food issue. It has been reported that FB1 is related to chronic kidney disease of unknown etiology. However, the study of FB1-induced nephrotoxicity in vitro is very limited and the mechanism is unknown. Human renal tubule epithelial (HK-2) cells were used in this study. The results showed that FB1 exposure could decrease cell viability, induce cell apoptosis and up-regulate the expression of Kim-1, collagen I, α-SMA and TGF-β1. In addition, autophagy was activated after FB1 exposure, including the conversion of LC3 and up-regulation of ATGs. Furthermore, autophagy inhibitor 3-MA could block FB1-induced abnormalities. And antioxidant enzymes (Gpx1 and Gpx4) were obviously down-regulated and intracellular ROS levels displayed an ascent trend as FB1 exposure concentrations increased. Employing of antioxidant NAC could suppress FB1-induced nephrotoxicity and autophagy. FB1 inhibited the phosphorylation of p70 S6k, a downstream protein of mTORC1. Also, oxidative stress, autophagy and phosphorylation of p70 S6k induced by FB1 was inhibited by MHY1485, an activator of mTOR. But the phosphorylation of AKT, a downstream protein of mTORC2 showed no change with or without MHY1485. Taken together, FB1 induced nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in HK-2 cells. Graphical abstract: Image 1 Highlights: FB1 exposure induced nephrotoxicity and oxidative stress in HK-2 cells. FB1 exposure could activate autophagy in HK-2 cells. FB1 induced nephrotoxicity via autophagy mediated by mTORC1 in HK-2 cells.