The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress

Afonso Ribeiro, Steven E. Bronk, Patricia J. Roberts, Raul Urrutia, Gregory J. Gores

Research output: Contribution to journalArticle

132 Citations (Scopus)

Abstract

Transforming growth factor β1 (TGF-β1)-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-β1-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-β1-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-β1-induced apoptosis. Both TGF-β1- 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-β1, TIEG1 induces apoptosis by a mechanism involving the formation of reactive oxygen species.

Original languageEnglish
Pages (from-to)1490-1497
Number of pages8
JournalHepatology
Volume30
Issue number6
StatePublished - Dec 14 1999
Externally publishedYes

Fingerprint

Transforming Growth Factors
Oxidative Stress
Transcription Factors
Apoptosis
Reactive Oxygen Species
Cell Line
Mitochondrial Membrane Potential
Caspase 3
Glutathione
Cell Differentiation
Pancreas
Cell Death
Antioxidants
Cell Proliferation

ASJC Scopus subject areas

  • Hepatology

Cite this

Ribeiro, A., Bronk, S. E., Roberts, P. J., Urrutia, R., & Gores, G. J. (1999). The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress. Hepatology, 30(6), 1490-1497.

The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress. / Ribeiro, Afonso; Bronk, Steven E.; Roberts, Patricia J.; Urrutia, Raul; Gores, Gregory J.

In: Hepatology, Vol. 30, No. 6, 14.12.1999, p. 1490-1497.

Research output: Contribution to journalArticle

Ribeiro, A, Bronk, SE, Roberts, PJ, Urrutia, R & Gores, GJ 1999, 'The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress', Hepatology, vol. 30, no. 6, pp. 1490-1497.
Ribeiro A, Bronk SE, Roberts PJ, Urrutia R, Gores GJ. The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress. Hepatology. 1999 Dec 14;30(6):1490-1497.
Ribeiro, Afonso ; Bronk, Steven E. ; Roberts, Patricia J. ; Urrutia, Raul ; Gores, Gregory J. / The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress. In: Hepatology. 1999 ; Vol. 30, No. 6. pp. 1490-1497.
@article{0125d40535ce4faa96c28fa2291d80b6,
title = "The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress",
abstract = "Transforming growth factor β1 (TGF-β1)-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-β1-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-β1-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-β1-induced apoptosis. Both TGF-β1- 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-β1, TIEG1 induces apoptosis by a mechanism involving the formation of reactive oxygen species.",
author = "Afonso Ribeiro and Bronk, {Steven E.} and Roberts, {Patricia J.} and Raul Urrutia and Gores, {Gregory J.}",
year = "1999",
month = "12",
day = "14",
language = "English",
volume = "30",
pages = "1490--1497",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "6",

}

TY - JOUR

T1 - The transforming growth factor β1-inducible transcription factor, TIEG1, mediates apoptosis through oxidative stress

AU - Ribeiro, Afonso

AU - Bronk, Steven E.

AU - Roberts, Patricia J.

AU - Urrutia, Raul

AU - Gores, Gregory J.

PY - 1999/12/14

Y1 - 1999/12/14

N2 - Transforming growth factor β1 (TGF-β1)-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-β1-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-β1-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-β1-induced apoptosis. Both TGF-β1- 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-β1, TIEG1 induces apoptosis by a mechanism involving the formation of reactive oxygen species.

AB - Transforming growth factor β1 (TGF-β1)-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-β1-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-β1-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-β1-induced apoptosis. Both TGF-β1- 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-β1, TIEG1 induces apoptosis by a mechanism involving the formation of reactive oxygen species.

UR - http://www.scopus.com/inward/record.url?scp=0032696730&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032696730&partnerID=8YFLogxK

M3 - Article

C2 - 10573529

AN - SCOPUS:0032696730

VL - 30

SP - 1490

EP - 1497

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 6

ER -