Defect in ERK2 and p54(JNK) activation in aging mouse splenocytes.
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 p46(JNK) activation were not significantly modified, the kinetics of both ERK2 and p54(JNK) 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 p54(JNK). 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.
Li
Min
M
Center for Gerontological Research, MCP-Hahnemann University, Philadelphia, Pennsylvania, USA.
Torres
Claudio
C
Acuña-Castillo
Claudio
C
Walter
Robin
R
Gardner
Elizabeth M
EM
Murasko
Donna M
DM
Sierra
Felipe
F
D000375:Aging / Q000378:metabolism*; D000818:Animals; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism*; D048057:Mitogen-Activated Protein Kinase 10; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D013154:Spleen / Q000166:cytology* / Q000201:enzymology*
D048057:Mitogen-Activated Protein Kinase 10; D011505:Protein-Tyrosine Kinases; D019950:Mitogen-Activated Protein Kinase 1; D020928:Mitogen-Activated Protein Kinases