Aflatoxin B1-Induced COX-2 Expression Promotes Mitophagy and Contributes to Lipid Accumulation in Hepatocytes In Vitro and In Vivo

Ren, Xin-Lu1; Han, Peiyu2; Meng, Yiteng3,4

2020-07-20

10.1177/1091581820939081

INTERNATIONAL JOURNAL OF TOXICOLOGY   影响因子和分区

1091-5818

1092-874X

Aim: Aflatoxin B1 (AFB1) is hepatotoxic. Numerous studies have shown that mitochondria play an essential role in AFB1-induced steatosis. However, the mechanisms of AFB1-induced steatosis via mitochondria are still obscure. The present study aimed to confirm that AFB1 causes hepatocyte steatosis regulated by cyclooxygenase-2 (COX-2)-induced mitophagy, both in vivo and in vitro. Methods: Adult male C57BL/6 mice were randomly divided into control group with the same volume of peanut oil and exposure group administered 0.6 mg/kg AFB1 once in 2 days for 1 month. HepG2 and Cas9-PTGS2 cells were treated with 5 mu M AFB1 for 48 hours. Then, various indicators were evaluated. Results: Aflatoxin B1 causes liver injury and steatosis with increased alanine aminotransferase, aspartate aminotransferase, total cholesterol, total triglyceride levels in vivo and in vitro, and elevated lipid droplets in HepG2 cells. Cyclooxygenase-2 and mitophagy pathway were induced by AFB1 in both liver tissues and cultured HepG2 cells. Further studies have shown that knockout of COX-2 with the CRISPR/Cas9 system inhibited the AFB1-induced mitophagy and steatosis in HepG2 cells. Also, the inhibition of PTEN-induced putative kinase with RNA interference attenuated the AFB1-induced steatosis. Conclusions: The results of the current study suggested that AFB1 increases the expression of COX-2, which, in turn, elevates the level of mitophagy, thereby disrupting the normal mitochondrial lipid metabolism and causing steatosis. Thus, this study implies that COX-2 may be a potential target for therapy against AFB1-induced steatosis.

aflatoxin B1 COX-2 mitophagy steatosis

SCI

英语

通讯

Pharmacology & Pharmacy ; Toxicology

Pharmacology & Pharmacy ; Toxicology

WOS:000550754000001

SAGE PUBLICATIONS INC

Web of Science

1.Nanchang Univ, Queen Mary Coll, Nanchang, Jiangxi, Peoples R China
2.Jiangnan Univ, Wuxi Sch Med, Wuxi, Jiangsu, Peoples R China
3.Jinan Univ, Dept Gastroenterol, Shenzhen Peoples Hosp, Clin Med Coll 2, Shenzhen 518020, Guangdong, Peoples R China
4.Southern Univ Sci & Technol, Affiliated Hosp 1, Shenzhen 518020, Guangdong, Peoples R China

Ren, Xin-Lu,Han, Peiyu,Meng, Yiteng. Aflatoxin B1-Induced COX-2 Expression Promotes Mitophagy and Contributes to Lipid Accumulation in Hepatocytes In Vitro and In Vivo[J]. INTERNATIONAL JOURNAL OF TOXICOLOGY,2020.

Ren, Xin-Lu,Han, Peiyu,&Meng, Yiteng.(2020).Aflatoxin B1-Induced COX-2 Expression Promotes Mitophagy and Contributes to Lipid Accumulation in Hepatocytes In Vitro and In Vivo.INTERNATIONAL JOURNAL OF TOXICOLOGY.

Ren, Xin-Lu,et al."Aflatoxin B1-Induced COX-2 Expression Promotes Mitophagy and Contributes to Lipid Accumulation in Hepatocytes In Vitro and In Vivo".INTERNATIONAL JOURNAL OF TOXICOLOGY (2020).