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a Center for Gerontological Research, MCP-Hahnemann University, Philadelphia, Pennsylvania
b Department of Microbiology and Immunology, MCP-Hahnemann University, Philadelphia, Pennsylvania
c Cell and Molecular Biology Program, Institute for Biomedical Sciences, School of Medicine, University of Chile, Santiago
Felipe Sierra, Lankenau Institute for Medical Research, 100 Lancaster Avenue, Wynnewood, PA 19096 E-mail: sierraf{at}mlhs.org.
Decision Editor: Edward J. Masoro, PhD
We have previously reported on a defect in both extracellular signal-regulated protein kinase (ERK) and c-jun N-terminal kinase (JNK) mitogen-activated protein kinase (MAPK) activation in splenocytes obtained from old rats. In order to investigate whether these effects are conserved across species, we have now used mouse splenocytes to measure the effect of aging on the activation of the same two MAPK families: ERK and JNK. Our results demonstrate that, as in rats, both MAPK signal transduction pathways are affected by aging in mice, indicating the existence of a further defect located downstream of the receptor-proximal events. Whereas ERK1 and p46JNK activation were not significantly modified, the kinetics of both ERK2 and p54JNK activation and inactivation were affected in splenocytes from old animals. Specifically, by analyzing the kinetics of activation and inactivation of these enzymes, we found a nearly 50% decrease in the fold of activation of both ERK2 and p54JNK. These defects result in an overall diminution of enzyme activities without changes in the steady-state levels of relevant proteins. The impaired activity of these two MAPK pathways is likely to play a role in the reduced expression of interleukin-2 and diminished lymphoproliferation observed in old animals.
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E. D. Boehmer, J. Goral, D. E. Faunce, and E. J. Kovacs Age-dependent decrease in Toll-like receptor 4-mediated proinflammatory cytokine production and mitogen-activated protein kinase expression J. Leukoc. Biol., February 1, 2004; 75(2): 342 - 349. [Abstract] [Full Text] [PDF] |
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