ITRAQ based quantitative proteomics analysis reveals that G6PD deficiency affects aflatoxin B1 metabolsim in A549 cells

Abstract

Glucose‐6‐phosphate dehydrogenase (G6PD), a metabolic enzyme in the pentose phosphate pathway, plays major roles in the regeneration of NADPH and maintenance of cellular redox status. In the present studies, we explored the effects of G6PD knockdown on global proteome change. Toward this end, we used G6PD‐knockdown A549 cells as the cell model to investigate the effects of altered redox status on proteome change by applying iTRAQ‐based LC‐MS/MS. In the iTRAQ analysis, 19 dysregulated proteins (5 proteins down‐regulated; 14 proteins up‐regulated) involved in metabolic pathway, protein folding and cellular component movement were identified in G6PD‐knockdown A549 cells compared to control ones. The data of RT‐PCR reveals that 3 down‐regulated genes; 8 up‐regulated genes are dysregulated at transcriptional level. Among them epoxide hydrolase 1 (EPHX1) was down‐regulated in G6PD‐knockdown cells which have been reported to be involved in regulating aflatoxin B1 (AFB1) metabolism. Indeed, increased susceptibility toward AFB1‐induced cell death were observed to accompany with decreased induction of EPHX1 in G6PD‐knockdown A549 cells compared to control ones. Take together, these data implicate that imbalanced redox status plays a role in regulating cellular detoxification of AFB1.