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

Abstract:

: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.

journal_name

Mol Carcinog

journal_title

Molecular carcinogenesis

authors

Adler V,Dolan LR,Kim J,Pincus M,Barrett JC,Ronai Z

doi

10.1002/(SICI)1098-2744(199609)17:1<8::AID-MC2>3.0

subject

Has Abstract

pub_date

1996-09-01 00:00:00

pages

8-12

issue

1

eissn

0899-1987

issn

1098-2744

pii

10.1002/(SICI)1098-2744(199609)17:1<8::AID-MC2>3.0

journal_volume

17

pub_type

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