5'-amp-activated Protein Kinase (Ampk) is Induced by Low-oxygen and Glucose Deprivation Conditions Found in Solid-tumor Microenvironments.
From: SRI International, Bldg. L, Rm. A258, 333 Ravenswood Ave., Menlo Park, CA 94025, USA. keith.laderoute@sri.com
Molecular and cellular biology
- Publish Date: Jul 2006
- ISSN: 0270-7306
- Volume: 26
- Issue: 14
- Pages: 5336-47
- Medium: Print
- Language: English
- Citation (JAMA): Laderoute Keith R, Amin Khalid, Calaoagan Joy M, et al. 5'-amp-activated Protein Kinase (Ampk) is Induced by Low-oxygen and Glucose Deprivation Conditions Found in Solid-tumor Microenvironments.. Mol. Cell. Biol. Jul 2006;26:5336-47
Abstract
Low oxygen gradients (hypoxia and anoxia) are important determinants of pathological conditions under which the tissue blood supply is deficient or defective, such as in solid tumors. We have been investigating the relationship between the activation of hypoxia-inducible factor 1 (HIF-1), the primary transcriptional regulator of the mammalian response to hypoxia, and 5’-AMP-activated protein kinase (AMPK), another regulatory system important for controlling cellular energy metabolism. In the present study, we used mouse embryo fibroblasts nullizygous for HIF-1alpha or AMPK expression to show that AMPK is rapidly activated in vitro by both physiological and pathophysiological low-oxygen conditions, independently of HIF-1 activity. These findings imply that HIF-1 and AMPK are components of a concerted cellular response to maintain energy homeostasis in low-oxygen or ischemic-tissue microenvironments. Finally, we used transformed derivatives of wild-type and HIF-1alpha- or AMPKalpha-null mouse embryo fibroblasts to determine whether AMPK is activated in vivo. We obtained evidence that AMPK is activated in authentic hypoxic tumor microenvironments and that this activity overlaps with regions of hypoxia detected by a chemical probe. We also showed that AMPK is important for the growth of this tumor model.
Mesh Headings (Keywords): Acetyl-CoA Carboxylase, Adenosine Triphosphate, Animals, Anoxia, Cells, Cultured, Enzyme Activation, Female, Genes, ras, Glucose, Hypoxia-Inducible Factor 1, alpha Subunit, Mice, Mice, Inbred BALB C, Mice, Knockout, Mice, Nude, Multienzyme Complexes, Neoplasms, Experimental, Phosphorylation, Protein-Serine-Threonine Kinases, Transformation, Genetic
Check for Full Text / PubMed Unique Identifier (PMID): 16809770
This abstract is part of PubMed, a service of the U.S. National Library of Medicine. PubMed includes more than 17 million citations from MEDLINE and other life science journals for biomedical articles. See Copyright and Disclaimers.
Linked medical terms appearing on this page are added by Healia to help readers find more information and are not part of the original PubMed document.
The data herein was last updated on July 8th, 2008 and may not reflect the most current and accurate data available from NLM.