Kulkarni, A PMittal, S PDevasagayam, T P APal, J K2011-11-142011-11-142010-04Kulkarni A P, Mittal S P, Devasagayam T P A, Pal J K. Hsp90 mediates activation of the heme regulated eIF-2 kinase during oxidative stress. Indian Journal of Biochemistry & Biophysics. 2010 Apr; 47(2): 67-74.http://imsear.searo.who.int/handle/123456789/135246The heme-regulated inhibitor (HRI), a member of the eIF-2 kinase family is crucial for regulating protein synthesis during stress. In addition to heme, stress proteins Hsp90 and Hsp70 are known to regulate HRI. The present study aims to determine the physical association of these Hsps in the regulation of HRI activation during oxidative stress using human K562 cells as a model. Extracts from the stress-induced cells were used for determining HRI kinase activity by measuring eIF-2 phosphorylation, and Hsp-HRI interaction by immunoprecipitation and immunoblot analyses. The results indicate a significant increase in both Hsp70 and Hsp90 expression during AAPH (2, 2’-azobis (2-amidinopropane) dihydrochloride)-induced oxidative stress. Further, their interaction with HRI, which correlates well with its increased HRI kinase activity leads to inhibition of protein synthesis. Thus, we demonstrate that Hsps play an important role in the regulation of initiation of protein synthesis during oxidative stress.eneIF-2 KinaseHsp70Hsp90Protein synthesisOxidative stressAmidines --chemistryAmidines --pharmacologyAnimalsEnzyme Activation --drug effectsHSP70 Heat-Shock Proteins --metabolismHSP90 Heat-Shock Proteins --metabolismHemin --pharmacologyHumansHydrophobic and Hydrophilic InteractionsIntracellular Space --drug effectsIntracellular Space --metabolismK562 CellsOxidative Stress --drug effectsPhosphorylation --drug effectsProtein Biosynthesis --drug effectsReactive Oxygen Species --metabolismArticle