Article (Scientific journals)
CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2.
Piret, Jean-Pascal; Mottet, Denis; Raes, Martine et al.
2002In Annals of the New York Academy of Sciences, 973, p. 443-7
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Keywords :
Apoptosis/drug effects/physiology; Carcinoma, Hepatocellular; Cell Death/drug effects/physiology; Cell Hypoxia/physiology; Cobalt/toxicity; Culture Media, Serum-Free; DNA-Binding Proteins/genetics; Helix-Loop-Helix Motifs; Humans; Hypoxia-Inducible Factor 1; Hypoxia-Inducible Factor 1, alpha Subunit; Liver Neoplasms; Nuclear Proteins/genetics; Transcription Factors; Tumor Cells, Cultured
Abstract :
[en] HIF-1 (hypoxia-inducible factor-1) is the major transcription factor that is specifically activated during hypoxia. This transcription factor is composed of two subunits: HIF-1alpha and ARNT (aryl hydrocarbon receptor nuclear translocator). ARNT is constitutively expressed, whereas HIF-1alpha is targeted to proteasome degradation by ubiquitination during normoxia. In hypoxia, HIF-1alpha is stabilized and translocates to the nucleus, where it binds to ARNT. The active HIF-1 induces expression of various genes whose products play an adaptive role to the new conditions induced by hypoxia. Besides the role played by HIF-1 in the adaptation to hypoxia, recent data describe a possible role for HIF-1 in the modulation of apoptosis. According to some authors, hypoxia induces apoptosis. However, it has also been reported that hypoxia could protect cells against apoptotic cell death induced by various agents such as serum deprivation and incubation in the presence of chemotherapy agents. These contradictory data suggest that HIF-1 could display either a proapoptotic or an antiapoptotic role according to the conditions. In order to study how HIF-1 can modulate apoptosis, we studied whether hypoxia or cobalt chloride, a chemical inducer of HIF-1, could influence apoptosis induced by tert-butyl hydroperoxide (t-BHP), serum deprivation, or both in hepatoma cell line HepG2. HepG2 cells were incubated 8 hours under normoxia or hypoxia in the presence of t-BHP with or without CoCl2. CoCl2 reduced the apoptotic death of HepG2 cells induced by t-BHP and serum deprivation, as measured by DNA fragmentation. This effect was confirmed by measurement of the caspase activity. Moreover, hypoxia also prevented t-BHP- or serum deprivation-induced DNA fragmentation and caspase activation-however, to a lower extent than CoCl2. These different data suggest a possible antiapoptotic role of HIF-1. More experiments are needed to define if HIF-1 actually plays an active role in cell death protection and to determine the exact mechanism underlying this effect.
Disciplines :
Biochemistry, biophysics & molecular biology
Oncology
Author, co-author :
Piret, Jean-Pascal
Mottet, Denis ;  Université de Liège - ULiège > Département des sciences biomédicales et précliniques > GIGA-R : Labo de recherche sur les métastases
Raes, Martine
Michiels, Carine
Language :
English
Title :
CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce apoptotic cell death in hepatoma cell line HepG2.
Publication date :
2002
Journal title :
Annals of the New York Academy of Sciences
ISSN :
0077-8923
eISSN :
1749-6632
Publisher :
New York Academy of Sciences, New York, United States - New York
Volume :
973
Pages :
443-7
Peer reviewed :
Peer Reviewed verified by ORBi
Funders :
FRIA - Fonds pour la Formation à la Recherche dans l'Industrie et dans l'Agriculture [BE]
F.R.S.-FNRS - Fonds de la Recherche Scientifique [BE]
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