TY - JOUR
T1 - Hypoxia-inducible Factor-2α (HIF-2α) Is Involved in the Apoptotic Response to Hypoglycemia but Not to Hypoxia
AU - Brusselmans, Koen
AU - Bono, Françoise
AU - Maxwell, Patrick
AU - Dor, Yuval
AU - Dewerchin, Mieke
AU - Collen, Désiré
AU - Herbert, Jean Marc
AU - Carmeliet, Peter
PY - 2001/10/19
Y1 - 2001/10/19
N2 - Deprivation of oxygen (hypoxia) and/or glucose (hypoglycemia) represents a serious stress that affects cellular survival. The hypoxia-inducible transcription factor-1α (HIF-1α), which has been implicated in the cellular response to hypoxia (Semenza, G. L. (1999) Annu. Rev. Cell Dev. Biol. 15, 551-578), mediates apoptosis during hypoxia (Halterman, M. W., Miller, C. C., and Federoff, H. J. (1999) J. Neurosci. 19, 6818-6824 and Carmeliet, P., Dor, Y., Herbert, J. M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., Koch, C. J., Ratcliffe, P., Moons, L., Jain, R. K., Collen, D., and Keshet, E. (1998) Nature 394, 485-490), but the function of its homologue HIF-2α remains unknown. Therefore, the role of HIF-2α in cellular survival was studied by targeted inactivation of the HIF-2α gene (HIF-2α-/-) in murine embryonic stem (ES) cells. In contrast to HIF-1α deficiency, loss of HIF-2α did not protect ES cells against apoptosis during hypoxia. Both HIF-1α -/- and HIF-2α-/- ES cells were, however, resistant to apoptosis in response to hypoglycemia. When co-cultured with wild type ES cells, HIF-2α-/- ES cells became rapidly and progressively enriched in hypoglycemia but not in hypoxia. Thus, HIF-1α and HIF-2α may have distinct roles in responses to environmental stress, and despite its name, HIF-2α may be more important in the survival response to environmental variables other than the level of oxygen.
AB - Deprivation of oxygen (hypoxia) and/or glucose (hypoglycemia) represents a serious stress that affects cellular survival. The hypoxia-inducible transcription factor-1α (HIF-1α), which has been implicated in the cellular response to hypoxia (Semenza, G. L. (1999) Annu. Rev. Cell Dev. Biol. 15, 551-578), mediates apoptosis during hypoxia (Halterman, M. W., Miller, C. C., and Federoff, H. J. (1999) J. Neurosci. 19, 6818-6824 and Carmeliet, P., Dor, Y., Herbert, J. M., Fukumura, D., Brusselmans, K., Dewerchin, M., Neeman, M., Bono, F., Abramovitch, R., Maxwell, P., Koch, C. J., Ratcliffe, P., Moons, L., Jain, R. K., Collen, D., and Keshet, E. (1998) Nature 394, 485-490), but the function of its homologue HIF-2α remains unknown. Therefore, the role of HIF-2α in cellular survival was studied by targeted inactivation of the HIF-2α gene (HIF-2α-/-) in murine embryonic stem (ES) cells. In contrast to HIF-1α deficiency, loss of HIF-2α did not protect ES cells against apoptosis during hypoxia. Both HIF-1α -/- and HIF-2α-/- ES cells were, however, resistant to apoptosis in response to hypoglycemia. When co-cultured with wild type ES cells, HIF-2α-/- ES cells became rapidly and progressively enriched in hypoglycemia but not in hypoxia. Thus, HIF-1α and HIF-2α may have distinct roles in responses to environmental stress, and despite its name, HIF-2α may be more important in the survival response to environmental variables other than the level of oxygen.
UR - http://www.scopus.com/inward/record.url?scp=0035914436&partnerID=8YFLogxK
U2 - 10.1074/jbc.C100428200
DO - 10.1074/jbc.C100428200
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C2 - 11546756
AN - SCOPUS:0035914436
SN - 0021-9258
VL - 276
SP - 39192
EP - 39196
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 42
ER -