Premium
The transforming growth factor β 1 –inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress
Author(s) -
Ribeiro Afonso,
Bronk Steven F.,
Roberts Patricia J.,
Urrutia Raul,
Gores Gregory J.
Publication year - 1999
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.510300620
Subject(s) - apoptosis , reactive oxygen species , transcription factor , microbiology and biotechnology , ap 1 transcription factor , transforming growth factor beta , programmed cell death , oxidative stress , transforming growth factor , chemistry , cancer research , biology , biochemistry , gene
Transforming growth factor β 1 (TGF‐β 1 )–inducible transcription factors have recently elicited interest because of their critical role in the regulation of cell proliferation, differentiation, and apoptosis. We have previously reported that the TGF‐β 1 –inducible transcription factor, TIEG1, induces apoptosis in a pancreas‐derived cell line. However, the mechanisms underlying the apoptotic effects of this transcription factor remain to be defined. In this study, using the TGF‐β 1 –sensitive Hep 3B cell line, we have defined the mechanistic sequence of events that characterize TIEG1‐mediated apoptosis and compared these events with the changes observed during TGF‐β 1 –induced apoptosis. Both TGF‐β 1 – and TIEG1‐induced cell death were accompanied by an increase in the generation of reactive oxygen species and a loss of the mitochondrial membrane potential preceding the morphological changes of apoptosis. In contrast, increases in caspase 3–like activity and glutathione (GSH) depletion occurred later in the apoptotic process, concurrent with the morphological features of apoptosis. The antioxidant, trolox, decreased the formation of reactive oxygen species and apoptosis. These results demonstrate that similar to TGF‐β 1 , TIEG1 induces apoptosis by a mechanism involving the formation of reactive oxygen species.