1. Academic Validation
  2. Patulin disrupts SLC7A11-cystine-cysteine-GSH antioxidant system and promotes renal cell ferroptosis both in vitro and in vivo

Patulin disrupts SLC7A11-cystine-cysteine-GSH antioxidant system and promotes renal cell ferroptosis both in vitro and in vivo

  • Food Chem Toxicol. 2022 Aug;166:113255. doi: 10.1016/j.fct.2022.113255.
Hui Chen 1 Lixing Cao 1 Kai Han 1 Han Zhang 1 Jinling Cui 1 Xuan Ma 1 Shuang Zhao 1 Chong Zhao 1 Shutao Yin 1 Lihong Fan 2 Hongbo Hu 3
Affiliations

Affiliations

  • 1 College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China.
  • 2 College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China. Electronic address: flh@cau.edu.cn.
  • 3 College of Food Science and Nutritional Engineering, China Agricultural University, Beijing, 100083, China. Electronic address: hongbo@cau.edu.cn.
Abstract

Patulin (PAT) is a common food-borne mycotoxin with diverse toxic effects including nephrotoxicity. The induction of oxidative stress is suggested to be a key mechanism contributed to toxicities of PAT. Reduced glutathione (GSH), a sulfhydryl-containing tripeptide, is a key reason for PAT-mediated oxidative stress. Cystine/glutamate antiporter (system xc-)-mediated cystine uptake plays a critical role in maintaining redox balance via promoting GSH biosynthesis. In this study, we addressed if GSH reduction by PAT was associated with inhibition of system xc--mediated GSH biosynthesis. Results showed that PAT significantly decreased activity of SLC7A11, a core subunit of system xc-, through activating AMPK-mediated formation of beclin1-SLC7A11 complex. Furthermore, PAT promoted Ferroptosis induced by a known Ferroptosis inducer RSL3 in normal renal cells, and exacerbated folic acid-induced nephrotoxicity in a mouse model of acute kidney injury. The findings of the present study provide new insights into PAT-induced kidney toxicity, and implicate that patients with ferroptosis-associated diseases maybe more susceptible to PAT.

Keywords

Ferroptosis; Nephrotoxicity; Patulin; SLC7A11; beclin1.

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