Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells

Lili Hou; Xin Yuan; Guannan Le; Ziman Lin; Fang Gan; Haolei Li; Kehe Huang

doi:10.1016/j.fct.2021.112037

Fumonisin B1 induces nephrotoxicity via autophagy mediated by mTORC1 instead of mTORC2 in human renal tubule epithelial cells

Food Chem Toxicol. 2021 Mar:149:112037. doi: 10.1016/j.fct.2021.112037. Epub 2021 Feb 3.

Authors

Lili Hou¹, Xin Yuan¹, Guannan Le¹, Ziman Lin¹, Fang Gan¹, Haolei Li¹, Kehe Huang²

Affiliations

¹ College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China.
² College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; Institute of Nutritional and Metabolic Disorders in Domestic Animals and Fowls, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China; MOE Joint International Research Laboratory of Animal Health and Food Safety, College of Veterinary Medicine, Nanjing Agricultural University, Nanjing, Jiangsu Province, 210095, China. Electronic address: khhuang@njau.edu.cn.

PMID: 33548371
DOI: 10.1016/j.fct.2021.112037

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.

Keywords: Autophagy; Fumonisin B1; HK-2 cells; Nephrotoxicity; Oxidative stress; mTORC1.

MeSH terms

Autophagic Cell Death / drug effects
Autophagy / drug effects*
Cell Line
Cell Survival / drug effects
Epithelial Cells / drug effects*
Fumonisins / toxicity*
Humans
Kidney Diseases / chemically induced*
Kidney Tubules / cytology*
Mechanistic Target of Rapamycin Complex 1 / genetics
Mechanistic Target of Rapamycin Complex 1 / metabolism*
Oxidative Stress / drug effects

Substances

Fumonisins
fumonisin B1
Mechanistic Target of Rapamycin Complex 1