Hsp90 mediates activation of the heme regulated eIF-2 alpha kinase during oxidative stress.
The heme-regulated inhibitor (HRI), a member of the eIF-2 alpha 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 alpha 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.
Department of Biotechnology, University of Pune, Pune 411 007, India.
A P
AP
Kulkarni
S P
SP
Mittal
T P A
TP
Devasagayam
J K
JK
Pal
D000578:Amidines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000378:metabolism*; D006427:Hemin / Q000494:pharmacology; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D020014:K562 Cells; D018384:Oxidative Stress / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D014176:Protein Biosynthesis / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D019892:eIF-2 Kinase / Q000378:metabolism*
D000578:Amidines; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D017382:Reactive Oxygen Species; C046728:2,2'-azobis(2-amidinopropane); D006427:Hemin; D019892:eIF-2 Kinase