Navigation auf zora.uzh.ch

Search ZORA

ZORA (Zurich Open Repository and Archive)

Normoxic induction of the hypoxia-inducible factor 1alpha by insulin and interleukin-1beta involves the phosphatidylinositol 3-kinase pathway.

Stiehl, D P; Jelkmann, W; Wenger, R H; Hellwig-Bürgel, T (2002). Normoxic induction of the hypoxia-inducible factor 1alpha by insulin and interleukin-1beta involves the phosphatidylinositol 3-kinase pathway. FEBS Letters, 512(1-3):157-162.

Abstract

Hypoxia-inducible factor 1 (HIF-1) is a heterodimeric DNA-binding complex of the subunits alpha and beta with relevance in O(2) and energy homeostasis. The labile component, HIF-1alpha, is not only activated by hypoxia but also by peptides such as insulin and interleukin-1 (IL-1) in normoxia. We investigated whether inhibitors of mitogen-activated protein kinase kinases (MAPKKs: PD 98059, U0126) and phosphatidylinositol 3-kinase (PI3K: LY 294002) do not only lower the hypoxia-induced, but also the insulin- and IL-1-induced HIF-1alpha accumulation and HIF-1 DNA-binding in human hepatoma cell cultures (line HepG2). The results show that LY 294002 suppressed HIF-1 activation in a dose-dependent manner irrespective of the stimulus. With respect to target proteins controlled by HIF-1, the production of erythropoietin was fully blocked and that of vascular endothelial growth factor reduced following inhibition of the PI3K pathway. The role of MAPKKs in this process remained in question, because PD 98059 and U0126 did not significantly reduce HIF-1alpha levels at non-toxic doses. We propose that PI3K signaling is not only important in the hypoxic induction of HIF-1 but it is also crucially involved in the response to insulin and IL-1.

Additional indexing

Item Type:Journal Article, refereed
Communities & Collections:04 Faculty of Medicine > Institute of Physiology
07 Faculty of Science > Institute of Physiology
Dewey Decimal Classification:570 Life sciences; biology
Scopus Subject Areas:Life Sciences > Biophysics
Life Sciences > Structural Biology
Life Sciences > Biochemistry
Life Sciences > Molecular Biology
Life Sciences > Genetics
Life Sciences > Cell Biology
Language:English
Date:2002
Deposited On:11 Feb 2008 12:22
Last Modified:01 Nov 2024 02:36
Publisher:Elsevier
ISSN:0014-5793
OA Status:Closed
Publisher DOI:https://doi.org/10.1016/S0014-5793(02)02247-0
PubMed ID:11852072
Full text not available from this repository.

Metadata Export

Statistics

Citations

Dimensions.ai Metrics
247 citations in Web of Science®
261 citations in Scopus®
Google Scholar™

Altmetrics

Authors, Affiliations, Collaborations

Similar Publications