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Cancer Cell death Cell cycle Cytoskeleton Exo/endocytosis Differentiation Division Organelles Signalling Stem cells Trafficking
Cell Biology International (2009) 33, 49–56 (Printed in Great Britain)
Dual role of HIF-1α in delivering a survival or death signal in hypoxia exposed human K562 erythroleukemia cells
Viviana di Giacomoab, Monica Rapinod, Sebastiano Misciaa, Camillo Di Giulioc and Amelia Cataldiab*
aDipartimento di Biomorfologia, Università G. d' Annunzio, Chieti-Pescara, Italy
bCattedra di Anatomia Umana, Facoltà di Farmacia, Università G. d' Annunzio, Chieti-Pescara, Italy
cDipartimento di Scienze Mediche di Base ed Applicate, Università G. d' Annunzio, Chieti-Pescara, Italy
dIstituto di Genetica Molecolare del CNR, Unità di Chieti, Italy


Abstract

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 22h. 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 5h 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.


Key words: HIF-1α, CREB, p38MAPK, Hypoxia, K562 erythroleukemia cells.

*Corresponding author at: Dipartimento di Biomorfologia, Università G. d' Annunzio, Via dei Vestini 6, 66100 Chieti, Italy. Tel.: +39 0871 3554508; fax: +39 0871 574361.


Received 18 March 2008/23 July 2008; accepted 13 October 2008

doi:10.1016/j.cellbi.2008.10.014


ISSN Print: 1065-6995
ISSN Electronic: 1095-8355
Published by Portland Press Limited on behalf of the International Federation for Cell Biology (IFCB)