Overexpression of HIF-1a could partially protect K562 cells from 1, 4-benzoquinone induced toxicity by inhibiting ROS, apoptosis and enhancing glycolysis. (March 2019)

• Record Type: Journal Article
• Authors: Sun, Rongli; Meng, Xing; Pu, Yunqiu; Sun, Fengxia; Man, Zhaodi; Zhang, Juan; Yin, Lihong; Pu, Yuepu
• Is Part Of: Toxicology in vitro. Volume 55(2019)
• Page Start: 18
• Page End: 23
• Publication Date: 2019-03
• Subjects: 1, 4-BQ -- Toxicity -- HIF-1a -- ROS -- Apoptosis -- Glycolysis; HIF-1a hypoxia inducible factor-1a -- LD lactic acid -- PA pyruvic acid -- ROS reactive oxygen species -- HQ hydroquinone -- 1, 4-BQ 1, 4-benzoquinone -- AML acute myeloid leukemia -- CML chronic myelogenous leukemia -- PI propidium iodide -- DCFH-DA 2′, 7′-dichlorofluorescein diacetate -- Glut1 glucose transporter of erythrocytes -- Pgk1 phosphoglycerate kinase 1 -- Ldha lactate dehydrogenase A -- Pkm2 pyruvate kinase M2 -- Pdk1 3-phosphoinositide-dependent protein kinase-1 -- Pfkl 6-phosphofructokinase -- Pfkfb3 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3; Toxicity testing -- In vitro -- Periodicals; Toxicology -- Periodicals; 615.9
• DOI: 10.1016/j.tiv.2018.11.005
• Languages: English
• ISSNs: 0887-2333

Abstract

Abstract: 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. Highlights: Overexpression of HIF-1a partially protected K562 cells from 1, 4-BQ-induced toxicity. Overexpression of HIF-1a decreased 1, 4-BQ-induced ROS and apoptosis. Overexpression of HIF-1a enhanced glycolysis in K562 cells exposed to 1, 4-BQ.