Oxidative stress perturbs cell proliferation in human K562 cells by modulating protein synthesis and cell cycle.
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 H(2)O(2). 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-2alpha 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 p34(cdc2) 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.
Kulkarni
Abhijeet P
AP
Department of Biotechnology, University of Pune, Pune, 411 007, India.
Mittal
Smriti P K
SP
Devasagayam
Thomas P A
TP
Pal
Jayanta K
JK
D000578:Amidines / Q000494:pharmacology; D017209:Apoptosis / Q000502:physiology; D002453:Cell Cycle / Q000502:physiology; D048708:Cell Growth Processes / Q000502:physiology; D002470:Cell Survival / Q000502:physiology; D006801:Humans; D006861:Hydrogen Peroxide / Q000494:pharmacology; D020014:K562 Cells; D004915:Leukemia, Erythroblastic, Acute / Q000378:metabolism* / Q000473:pathology*; D018384:Oxidative Stress / Q000502:physiology*; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis
D000578:Amidines; C046728:2,2'-azobis(2-amidinopropane); D006861:Hydrogen Peroxide