Changes in jun N-terminal kinase activation by stress during aging of cultured normal human fibroblasts.
The molecular changes associated with the aging process include the reduced activity of transcription factors (such as AP-1) and an impaired response to stress, which has been well documented in the case of the heat-shock (HS) response. Using human diploid fibroblasts of early and late passages as an in vitro model for aging, we elucidated changes in the activation of jun N-terminal kinases (JNKs), which play an important role in the mammalian stress response. We found that early-passage cells exhibited a greater degree of JNK activation in response to HS and ultraviolet (UV) C light treatments than did late-passage cells. Decreased JNK activation was dependent on the number of passages but was not affected by varying doses of UV irradiation. Analysis of protein kinase A, mitogen-activated protein kinase, and src-related tyrosine kinases revealed no decreased activities in aged cells, indicating a selective rather than generalized decrease in kinase activities during aging. A further understanding of this impaired activation of JNK may provide insights into the mechanisms of stress response and cellular aging.
Adler
V
V
Molecular Carcinogenesis Program, American Health Foundation, Valhalla, NY 10595, USA.
Dolan
L R
LR
Kim
J
J
Pincus
M
M
Barrett
J C
JC
Ronai
Z
Z
D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D016922:Cellular Senescence; D004789:Enzyme Activation; D005347:Fibroblasts / Q000201:enzymology; D018869:Heat-Shock Response / Q000235:genetics*; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D013312:Stress, Physiological / Q000201:enzymology / Q000235:genetics*; D014466:Ultraviolet Rays
D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases