PMID- 12485908
OWN - NLM
STAT- MEDLINE
DCOM- 20030213
LR  - 20220408
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 973
DP  - 2002 Nov
TI  - CoCl2, a chemical inducer of hypoxia-inducible factor-1, and hypoxia reduce 
      apoptotic cell death in hepatoma cell line HepG2.
PG  - 443-7
AB  - 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.
FAU - Piret, Jean-Pascal
AU  - Piret JP
AD  - Laboratoire de Biologie et Biochimie cellulaire, FUNDP, 5000 Namur, Belgium. 
      jppiret@fundp.ac.be
FAU - Mottet, Denis
AU  - Mottet D
FAU - Raes, Martine
AU  - Raes M
FAU - Michiels, Carine
AU  - Michiels C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (HIF1A protein, human)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Transcription Factors)
RN  - 3G0H8C9362 (Cobalt)
RN  - EVS87XF13W (cobaltous chloride)
SB  - IM
MH  - Apoptosis/drug effects/*physiology
MH  - Carcinoma, Hepatocellular
MH  - Cell Death/drug effects/physiology
MH  - Cell Hypoxia/*physiology
MH  - Cobalt/*toxicity
MH  - Culture Media, Serum-Free
MH  - DNA-Binding Proteins/*genetics
MH  - Helix-Loop-Helix Motifs
MH  - Humans
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Liver Neoplasms
MH  - Nuclear Proteins/*genetics
MH  - *Transcription Factors
MH  - Tumor Cells, Cultured
EDAT- 2002/12/18 04:00
MHDA- 2003/02/14 04:00
CRDT- 2002/12/18 04:00
PHST- 2002/12/18 04:00 [pubmed]
PHST- 2003/02/14 04:00 [medline]
PHST- 2002/12/18 04:00 [entrez]
AID - 10.1111/j.1749-6632.2002.tb04680.x [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2002 Nov;973:443-7. doi: 10.1111/j.1749-6632.2002.tb04680.x.