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Dual role of HIF-1α in delivering a survival or death signal in hypoxia exposed human K562 erythroleukemia cells


Dipartimento di Biomorfologia, Università G. d' Annunzio, Via dei Vestini 6, 66100 Chieti, Italy. Tel.: +39 0871 3554508; fax: +39 0871 574361. E-mail addresses:


Hypoxia (reduced oxygen tension) is a critical stimulus which switches on a cell rapid response, determining damage and death in some cells, and adaptation and survival in others. Here we report that K562 erythroleukemia cells exposed to hypoxia, proliferated more slowly and the percentage of dead cells increased after 22 h. In parallel HIF (Hypoxia Inducible Factor)-1α and Bax level increased, as well as the PKC (Protein Kinase C) δ/Erk (Extracellular Signal Regulated Kinase) pathways being activated. The low level of ROS after 5 h of hypoxia did not modify cell cycle progression or affect cell death, whereas HIF-1α/CBP (CREB Binding Protein) co-immunoprecipitation and MAPK (Mitogen Activated Protein Kinase)/CREB (c-AMP Response Element Binding) protein signalling pathway activation determined the adaptive survival response. We suggest a dual role for HIF-1α in providing a survival or death signal, based on hypoxia duration, and consider the nuclear transcription factor, CREB, to be a possible target for hypoxic therapy against leukemia disease.