Tissue specific expression of PKR protein kinase in aging B6D2F1 mice.
A decline in the rate of protein synthesis is a common biochemical change observed with aging in a wide variety of cells and organisms. The double stranded RNA-dependent protein kinase PKR has been shown to phosphorylate eukaryotic initiation factor 2 alpha (eIF-2alpha), a well-characterized factor for down-regulating protein synthesis, in response to environmental stress conditions. Therefore, we were interested in evaluating the role of PKR in the aging process. Tissues from 2- and 20-month-old B6D2F1 male mice were evaluated by Western blot analysis. PKR was detected in all tissues of aging mice confirming its ubiquitous nature. Tissues examined from young mice showed little evidence of PKR expression, suggesting an age-associated up-regulation. P58(IPK), a cellular inhibitor of PKR, was expressed in tissues from both age groups but to a greater extent in tissues of aging mice suggesting an up-regulation to control PKR activity. Hyperphosphorylated eIF-2alpha was increased in selected tissues from older mice compared with tissues from younger mice indicating a possible correlation between PKR expression and kinase function. The data suggest that translational activity is slowing down in a tissue specific manner during the aging process in mice, possibly as the result of increased levels of PKR, and could be a factor in the reduction of the rate of protein synthesis during senescence seen in specific tissues of many organisms.
Ladiges
W
W
The Nathan Shock Center for Excellence in the Biology of Aging, School of Medicine, University of Washington, Seattle, WA 98195, USA. wladiges@u.washington.edu
Morton
J
J
Blakely
C
C
Gale
M
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D015852:Eukaryotic Initiation Factor-2 / Q000096:biosynthesis; D050956:HSP40 Heat-Shock Proteins; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D012097:Repressor Proteins / Q000096:biosynthesis; D014018:Tissue Distribution; D019892:eIF-2 Kinase / Q000096:biosynthesis*
C500846:Dnajc3 protein, mouse; D015852:Eukaryotic Initiation Factor-2; D050956:HSP40 Heat-Shock Proteins; D012097:Repressor Proteins; D019892:eIF-2 Kinase