Metformin alleviates nickel-refining fumes-induced aerobic glycolysis via AMPK/GOLPH3 pathway in vitro and in vivo

Ecotoxicology and Environmental Safety

Yonghui Wu¹  Dan Zhang²  Shuo Jin²  Wenxue Yao²  Tong Zhang²  Yangyang Chen²  Shikuan Yang²  Ying Gao²  Lina Li²  Yue Wang² 

[1] Correspondence to: Department of Occupational Health, College of Public Health, Harbin Medical University, No. 157 Baojian Road, Nangang District, Harbin 150081, PR China.;Department of Occupational Health, College of Public Health, Harbin Medical University, Harbin, Heilongjiang Province 150086, PR China;

关键词: Nickel-refining fumes;    GOLPH3;    Aerobic glycolysis;    AMPK;    Metformin;   

DOI  :  

来源: DOAJ

【 摘 要 】

Nickel (Ni) compounds is recognized industrial carcinogen, which could increase the risk of lung cancer in Ni refineries workers. However, the underlying carcinogenic mechanism still remains to elucidate. Metformin has shown the anticancer properties through suppressing aerobic glycolysis. In the present study, we evaluated the effect of Ni-refining fumes exposure on aerobic glycolysis and the role of AMPK/GOLPH3, as well as how metformin alleviated nickel-induced aerobic glycolysis in vitro and vivo. Firstly, Beas-2B cells were exposed to different concentrations of Ni-refining fumes and pretreated with metformin (activation of AMPK), compound C (AMPK inhibitor) in vitro. Our findings indicated that Ni fumes expose evoked aerobic glycolysis by AMPK/GOLPH3, while metformin attenuated Ni particles-promoted GOLPH3-mediated aerobic glycolysis by p-AMPK expression increase. Then Mito-TEMPT (a mitochondria-targeted antioxidant) and lipopolysaccharide (LPS, ROS activator) were pretreated to affect ROS production in Beas-2B cells. Ni-induced ROS prevented AMPK activation. Moreover, C57BL/6 mice were exposed to 2 mg/kg Ni by non-exposed endotracheal instillation and metformin (100, 200 and 300 mg/kg) via oral gavage for 4 weeks. The effects of AMPK/GOLPH3 axis on Ni-induced aerobic glycolysis were assessed. The results indicated that metformin decreased the protein levels of GOLPH3, LDHA, HK2, MCT-4 and improved p-AMPK expression. Thus, our findings demonstrated metformin antagonized Ni-refining fumes-caused aerobic glycolysis via AMPK/GOLPH3.

【 授权许可】

Unknown