Overexpression of HIF-1a could partially protect K562 cells from 1,4-benzoquinone induced toxicity by inhibiting ROS, apoptosis and enhancing glycolysis

Add time:08/31/2019    Source:sciencedirect.com

Benzene is an environmental contaminant which causes hematological diseases. Previously, hypoxia inducible factor-1a (HIF-1a) was found to be involved in benzene-induced hematotoxicity. This study aims to explore whether overexpression of HIF-1a in K562 cell line could influence the toxicity caused by 1,4-BQ. HIF-1a overexpression K562 cell line was constructed with a lentiviral vector. Results showed that HIF-1a was significantly elevated in control K562 cells and HIF-1a overexpression cells exposed to 1,4-BQ. Compared with 1,4-BQ exposed control cells, HIF-1a overexpression blocked cell cycle at G2/M phase, remarkably reduced apoptosis and ROS level. And HIF-1a overexpression caused downregulation of Nox4 and upregulation of Bcl-2. In addition, the lactic acid (LD)/pyruvic acid (PA) ratio was significantly higher in HIF-1a overexpression cells than that in control cells at the same 1,4-BQ dose. Furthermore, significant increases in Glut1, Ldha, Pkm2, Pgk1, Pdk1, Pfkl, Pfkfb3 protein levels was also observed in HIF-1a overexpression cells. Overall, our results indicated that HIF-1a overexpression could alleviate ROS and apoptosis caused by 1,4-BQ through targeting Nox4, Bcl-2 and key enzymes in glycolysis.

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