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Changes in jun N-terminal kinase activation by stress during aging of cultured normal human fibroblasts

✍ Scribed by Victor Adler; Lisa R. Dolan; Jeanette Kim; Matthew Pincus; J. Carl Barrett; Zeev Ronai

Publisher: John Wiley and Sons
Year: 1996
Tongue: English
Weight: 606 KB
Volume: 17
Category: Article
ISSN: 0899-1987
DOI: 10.1002/(sici)1098-2744(199609)17:1<8::aid-mc2>3.0.co;2-f

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✦ Synopsis

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 heatshock (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 J N K may provide insights into the mechanisms of stress response and cellular aging.

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