Inhibition of Glucose‐6‐Phosphate Dehydrogenase Could Enhance 1,4‐Benzoquinone‐Induced Oxidative Damage in K562 Cells

Abstract

Benzene is a chemical contaminant widespread in industrial and living environments. The oxidative metabolites of benzene induce toxicity involving oxidative damage. Protecting cells and cell membranes from oxidative damage, glucose-6-phosphate dehydrogenase (G6PD) maintains the reduced state of glutathione (GSH). This study aims to investigate whether the downregulation of G6PD in K562 cell line can influence the oxidative toxicity induced by 1,4-benzoquinone (BQ). G6PD was inhibited in K562 cell line transfected with the specific siRNA of G6PD gene. An empty vector was transfected in the control group. Results revealed that G6PD was significantly upregulated in the control cells and in the cells with inhibited G6PD after they were exposed to BQ. The NADPH/NADP and GSH/GSSG ratio were significantly lower in the cells with inhibited G6PD than in the control cells at the same BQ concentration. The relative reactive oxygen species (ROS) level and DNA oxidative damage were significantly increased in the cell line with inhibited G6PD. The apoptotic rate and G2 phase arrest were also significantly higher in the cells with inhibited G6PD and exposed to BQ than in the control cells. Our results suggested that G6PD inhibition could reduce GSH activity and alleviate oxidative damage. G6PD deficiency is also a possible susceptible risk factor of benzene exposure.

Endothelial function and dysfunction: Impact of metformin

“…G6PDH is inhibited by the hyperglycaemia-mediated increase in protein kinase A and is the rate limiting step in the pentose phosphate pathway (J. Zhang, et al, 2016). Reduced G6PD Blood levels of metformin are obviously relevant to the actions of metformin.…”

Cell Metabolism and DNA Repair Pathways: Implications for Cancer Therapy

“…Furthermore, a study showed that Ataxia Telangiectasia Mutated (ATM), a key DNA damage protein, activates the PPP pathway through G6PD to promote antioxidant defense mechanisms and DNA repair activity via nucleotide production under stressed conditions ( Cosentino et al, 2011 ). This suggests that G6PD activity is likely to also be required for the repair of DNA damage and maintaining DNA integrity ( Zhang et al, 2016 ).…”

Antitumour Effects of Astaxanthin and Adonixanthin on Glioblastoma

“…Furthermore, astaxanthin and adonixanthin increased the expression of phosphorylated p38 ( Figure 4 C). The phosphorylation of p38 can lead to cell damage and cell cycle arrest [ 30 ]. Therefore, the antitumour effects of both astaxanthin and adonixanthin were involved in increasing the expression of phosphorylated p38.…”

“…To elucidate the active site of both compounds, we examined their effect on ROS, which is important for the regulation of both ERK1/2 and Akt phosphorylation [ 35 ]. In the past, it has been reported that ROS promote tumour progression via the phosphorylation of ERK1/2 and Akt [ 27 , 30 ]. Therefore, we evaluated the level of ROS in glioblastoma cells following treatment with both compounds for 6 h. Both compounds greatly reduced the levels of intracellular ROS ( Figure 5 A).…”