Dual role of HIF-1alpha in delivering a survival or death signal in hypoxia exposed human K562 erythroleukemia cells.
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)-1alpha and Bax level increased, as well as the PKC (Protein Kinase C) delta/Erk (Extracellular Signal Regulated Kinase) pathways being activated. The low level of ROS after 5h of hypoxia did not modify cell cycle progression or affect cell death, whereas HIF-1alpha/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-1alpha 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.
di Giacomo
Viviana
V
Dipartimento di Biomorfologia, Università G. d' Annunzio, Chieti-Pescara, Italy.
Rapino
Monica
M
Miscia
Sebastiano
S
Di Giulio
Camillo
C
Cataldi
Amelia
A
D017209:Apoptosis; D002453:Cell Cycle; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D002467:Cell Nucleus; D002470:Cell Survival; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D047468:Immunoprecipitation; D020014:K562 Cells; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D051745:Protein Kinase C-delta / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D015398:Signal Transduction; D013997:Time Factors; D051028:bcl-2-Associated X Protein / Q000378:metabolism
D017362:Cyclic AMP Response Element-Binding Protein; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D051745:Protein Kinase C-delta; D020928:Mitogen-Activated Protein Kinases