TY - JOUR
T1 - Enhanced sensitivity of protein kinase B/Akt to insulin in hypoxia is independent of HIF1 alpha and promotes cell viability
AU - Barry, R.E.
AU - Allan, B.B.
AU - Cummins, E.P.
AU - Kattla, J.J.
AU - Giblin, A.
AU - Scally, N.
AU - Taylor, C.T.
AU - Brazil, Derek
PY - 2007/7/27
Y1 - 2007/7/27
N2 - Maintenance of oxygen homeostasis is a key requirement to ensure normal mammalian cell growth and differentiation. Hypoxia arises when oxygen demand exceeds supply, and is a feature of multiple human diseases including stroke, cancer and renal fibrosis. We have investigated the effect of hypoxia on kidney cells, and observed that insulin-induced cell viability is increased in hypoxia. We have characterized the role of protein kinase B (PKB/ Akt) in these cells as a potential mediator of this effect. PKB/Akt activity was increased by low oxygen concentrations in kidney cells, and insulin-stimulated activation of PKB/Akt was stronger, more rapid and more sustained in hypoxia. Reduction of HIF1 alpha levels using antimycin-A or siRNA targeting HlF1 alpha did not affect PKB/Akt activation in hypoxia. Pharmacologic stabilization of HIF1 alpha independent of hypoxia did not increase insulin-stimulated PKB/Akt activation. Although increased insulin-stimulated cell viability was observed in hypoxia, no differences in the degree of insulin-stimulated glucose uptake were observed in L6 muscle cells in hypoxia compared to normoxia. Thus, PKB/Akt may regulate specific cellular responses to growth factors such as insulin under adverse conditions such as hypoxia. alpha 2007 Elsevier GmbH. All rights reserved.
AB - Maintenance of oxygen homeostasis is a key requirement to ensure normal mammalian cell growth and differentiation. Hypoxia arises when oxygen demand exceeds supply, and is a feature of multiple human diseases including stroke, cancer and renal fibrosis. We have investigated the effect of hypoxia on kidney cells, and observed that insulin-induced cell viability is increased in hypoxia. We have characterized the role of protein kinase B (PKB/ Akt) in these cells as a potential mediator of this effect. PKB/Akt activity was increased by low oxygen concentrations in kidney cells, and insulin-stimulated activation of PKB/Akt was stronger, more rapid and more sustained in hypoxia. Reduction of HIF1 alpha levels using antimycin-A or siRNA targeting HlF1 alpha did not affect PKB/Akt activation in hypoxia. Pharmacologic stabilization of HIF1 alpha independent of hypoxia did not increase insulin-stimulated PKB/Akt activation. Although increased insulin-stimulated cell viability was observed in hypoxia, no differences in the degree of insulin-stimulated glucose uptake were observed in L6 muscle cells in hypoxia compared to normoxia. Thus, PKB/Akt may regulate specific cellular responses to growth factors such as insulin under adverse conditions such as hypoxia. alpha 2007 Elsevier GmbH. All rights reserved.
UR - http://www.scopus.com/inward/record.url?scp=34250866182&partnerID=8YFLogxK
U2 - 10.1016/j.ejcb.2007.04.006
DO - 10.1016/j.ejcb.2007.04.006
M3 - Article
VL - 86
SP - 393
EP - 403
JO - European Journal of Cell Biology
JF - European Journal of Cell Biology
IS - 7
ER -