Sedoheptulose-1, 7-bisphospate Accumulation and Metabolic Anomalies in Hepatoma Cells Exposed to Oxidative Stress. (13th January 2019)

• Record Type: Journal Article
• Authors: Cheng, Mei-Ling; Lin, Jui-Fen; Huang, Cheng-Yu; Li, Guan-Jie; Shih, Lu-Min; Chiu, Daniel Tsun-Yee; Ho, Hung-Yao
• Other Names: Bartosz Grzegorz Academic Editor.
• Is Part Of: Oxidative medicine and cellular longevity. Volume 2019(2019)
• Publication Date: 2019-01-13
• Subjects: Oxidative stress -- Periodicals; Cells -- Aging -- Periodicals; Cells -- Aging; Oxidative stress; Oxidative Stress -- Periodicals; Cell Aging -- Periodicals; Periodicals; 611.0181
• DOI: 10.1155/2019/5913635
• Languages: English
• ISSNs: 1942-0900

Abstract

Abstract : We have previously shown that GSH depletion alters global metabolism of cells. In the present study, we applied a metabolomic approach for studying the early changes in metabolism in hydrogen peroxide- (H2 O2 -) treated hepatoma cells which were destined to die. Levels of fructose 1, 6-bisphosphate and an unusual metabolite, sedoheptulose 1, 7-bisphosphate (S-1, 7-BP), were elevated in hepatoma Hep G2 cells. Deficiency in G6PD activity significantly reduced S-1, 7-BP formation, suggesting that S-1, 7-BP is formed in the pentose phosphate pathway as a response to oxidative stress. Additionally, H2 O2 treatment significantly increased the level of nicotinamide adenine dinucleotide phosphate (NADP + ) and reduced the levels of ATP and NAD + . Severe depletion of ATP and NAD + in H2 O2 -treated Hep G2 cells was associated with cell death. Inhibition of PARP-mediated NAD + depletion partially protected cells from death. Comparison of metabolite profiles of G6PD-deficient cells and their normal counterparts revealed that changes in GSH and GSSG per se do not cause cell death. These findings suggest that the failure of hepatoma cells to maintain energy metabolism in the midst of oxidative stress may cause cell death.