- 作者: Wei-Cheng Chen, Shih-Rong Hsieh, Chun-Hwei Chiu, Ban-Dar Hsu, Ying-Ming Liou
- 作者服務機構: Institute of Bioinformatics and Structural Biology, National Tsing Hua university, Hsinchu , Taiwan R.O.C
- 中文摘要: --
- 英文摘要:
Background:
Epigallocatechin-3-gallate (EGCG) has been documented for its beneficial effects protecting oxidative stress to cardiac cells. Previously, we have shown the EGCG-mediated cardiac protection by attenuating reactive oxygen species and cytosolic Ca2+ in cardiac cells during oxidative stress and myocardial ischemia. Here, we aimed to seek a deeper elucidation of the molecular anti-oxidative capabilities of EGCG in an H2O2-induced oxidative stress model of myocardial ischemia injury using H9c2 rat cardiomyoblasts.
Results:
Proteomics analysis was used to determine the differential expression of proteins in H9c2 cells cultured in the conditions of control, 400 muM H2O2 exposure for 30 min with and/or without 10 to 20 muM EGCG pre-treatment. In this model, eight proteins associated with energy metabolism, mitochondrial electron transfer, redox regulation, signal transduction, and RNA binding were identified to take part in EGCG-ameliorating H2O2-induced injury in H9c2 cells. H2O2 exposure increased oxidative stress evidenced by increases in reactive oxygen species and cytosolic Ca2+ overload, increases in glycolytic protein, alpha-enolase, decreases in antioxidant protein, peroxiredoxin-4, as well as decreases in mitochondrial proteins, including aldehyde dehydrogenase-2, ornithine aminotransferase, and succinate dehydrogenase ubiquinone flavoprotein subunit. All of these effects were reversed by EGCG pre-treatment. In addition, EGCG attenuated the H2O2-induced increases of Type II inositol 3, 4-bisphosphate 4-phosphatase and relieved its subsequent inhibition of the downstream signalling for Akt and glycogen synthase kinase-3beta (GSK-3beta)/cyclin D1 in H9c2 cells. Pre-treatment with EGCG or GSK-3beta inhibitor (SB 216763) significantly improved the H2O2-induced suppression on cell viability, phosphorylation of pAkt (S473) and pGSK-3beta (S9), and level of cyclin D1 in cells.
Conclusions:
Collectively, these findings suggest that EGCG blunts the H2O2-induced oxidative effect on the Akt activity through the modulation of PIP3 synthesis leading to the subsequent inactivation of GSK-3beta mediated cardiac cell injury. - 中文關鍵字: --
- 英文關鍵字: EGCG, H9c2, Oxidative stress, Proteomics analysis, Survival pathway