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Abstract
Oxidative stress leads to perturbation of a variety of cellular processes resulting in inhibition of cell proliferation. This study has determined the effect of oxidative stress on protein synthesis in human K562 cells using a hydrophilic peroxyl radical initiator, AAPH and H2O2. The results indicated that oxidative stress leads to a significant decrease in the rate of protein synthesis caused due to induced activation as well as expression of the erythroid cell-specific eIF-2α kinase, called the Heme Regulated Inhibitor (HRI). Elevated levels of HRI expression and activity were accompanied by increased lipid peroxidation and decreased cell proliferation. Further, oxidative stress also caused inactivation of p34cdc2 kinase, thereby arresting cell division leading to apoptosis. Thus, the data provides the mechanism of inhibition of protein synthesis and perturbation of a cell cycle regulatory protein leading to inhibition of cell proliferation in K562 cells during oxidative stress.
| Abbreviations | ||
| AAPH | = | 2, 2′-azobis (2-amidinopropane) dihydrochloride |
| DCFH-DA | = | 2′, 7′-dichlorodihydrofluorescein diacetate |
| eIF-2B | = | eukaryotic initiation factor-2B |
| eIF-2α | = | eukaryotic initiation factor-2alpha |
| H2O2 | = | hydrogen peroxide |
| HRI | = | heme regulated inhibitor |
| LOOH | = | lipid hydroperoxide |
| MTT | = | 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide |
| p34cdc2 | = | cyclin dependent protein kinase 1 |
| SDS-PAGE | = | sodium dodecyl sulphate-polyacrylamide gel electrophoresis |
| Abbreviations | ||
| AAPH | = | 2, 2′-azobis (2-amidinopropane) dihydrochloride |
| DCFH-DA | = | 2′, 7′-dichlorodihydrofluorescein diacetate |
| eIF-2B | = | eukaryotic initiation factor-2B |
| eIF-2α | = | eukaryotic initiation factor-2alpha |
| H2O2 | = | hydrogen peroxide |
| HRI | = | heme regulated inhibitor |
| LOOH | = | lipid hydroperoxide |
| MTT | = | 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide |
| p34cdc2 | = | cyclin dependent protein kinase 1 |
| SDS-PAGE | = | sodium dodecyl sulphate-polyacrylamide gel electrophoresis |