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Human GSTA1 suppresses JNK activation and development of apoptosis
Author(s) -
Kirby Gordon M,
Romero Laura
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1123-a
Subject(s) - apoptosis , tunel assay , kinase , microbiology and biotechnology , stimulation , phosphorylation , butyrate , chemistry , c jun , biology , endocrinology , biochemistry , gene , transcription factor , fermentation
Glutathione S‐transferases are implicated in the regulation of c‐Jun‐NH2‐terminal kinase (JNK) activation, however, the role of GSTA1 has not been investigated. We tested the hypothesis that overexpression of human GSTA1 inhibits JNK activation by comparing c‐Jun phosphorylation in cells in which GSTA1 was variably expressed. JNK activation following exposure to IL‐1 beta, UV light or H2O2 was assessed in MEF/3T3 cells in which GSTA1 was controlled using a tet‐off expression system as well as in pre‐ and post‐confluent Caco‐2 cells with low and high GST expression respectively. JNK activation by all three stimuli was significantly less in cells in which GST expression was high. Moreover, the percentage of cells undergoing apoptosis, as assessed by TUNEL and caspase‐3 activation, following stimulation with butyrate and TNF alpha was 6 fold less in post‐confluent Caco‐2 cells compared to pre‐confluent cells. These findings indicate that GSTA1 plays an important modulating role in controlling JNK activity and the associated consequences of cellular stress. Supported by the Canadian Institutes for Health Research