Document Detail


Analysis of hypoxia and hypoxia-like states through metabolite profiling.
MedLine Citation:
PMID:  21931840     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
BACKGROUND: In diverse organisms, adaptation to low oxygen (hypoxia) is mediated through complex gene expression changes that can, in part, be mimicked by exposure to metals such as cobalt. Although much is known about the transcriptional response to hypoxia and cobalt, little is known about the all-important cell metabolism effects that trigger these responses.
METHODS AND FINDINGS: Herein we use a low molecular weight metabolome profiling approach to identify classes of metabolites in yeast cells that are altered as a consequence of hypoxia or cobalt exposures. Key findings on metabolites were followed-up by measuring expression of relevant proteins and enzyme activities. We find that both hypoxia and cobalt result in a loss of essential sterols and unsaturated fatty acids, but the basis for these changes are disparate. While hypoxia can affect a variety of enzymatic steps requiring oxygen and heme, cobalt specifically interferes with diiron-oxo enzymatic steps for sterol synthesis and fatty acid desaturation. In addition to diiron-oxo enzymes, cobalt but not hypoxia results in loss of labile 4Fe-4S dehydratases in the mitochondria, but has no effect on homologous 4Fe-4S dehydratases in the cytosol. Most striking, hypoxia but not cobalt affected cellular pools of amino acids. Amino acids such as aromatics were elevated whereas leucine and methionine, essential to the strain used here, dramatically decreased due to hypoxia induced down-regulation of amino acid permeases.
CONCLUSIONS: These studies underscore the notion that cobalt targets a specific class of iron proteins and provide the first evidence for hypoxia effects on amino acid regulation. This research illustrates the power of metabolite profiling for uncovering new adaptations to environmental stress.
Authors:
Julie E Gleason; David J Corrigan; James E Cox; Amit R Reddi; Lauren A McGinnis; Valeria C Culotta
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2011-09-12
Journal Detail:
Title:  PloS one     Volume:  6     ISSN:  1932-6203     ISO Abbreviation:  PLoS ONE     Publication Date:  2011  
Date Detail:
Created Date:  2011-09-20     Completed Date:  2012-02-28     Revised Date:  2013-06-27    
Medline Journal Info:
Nlm Unique ID:  101285081     Medline TA:  PLoS One     Country:  United States    
Other Details:
Languages:  eng     Pagination:  e24741     Citation Subset:  IM    
Affiliation:
Department of Biochemistry and Molecular Biology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, Maryland, United States of America.
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MeSH Terms
Descriptor/Qualifier:
Cell Hypoxia / drug effects,  physiology*
Chromatography, Gas
Cobalt / pharmacology
Fatty Acids / metabolism
Gas Chromatography-Mass Spectrometry
Immunoblotting
Saccharomyces cerevisiae / drug effects,  metabolism
Sterols / metabolism
Grant Support
ID/Acronym/Agency:
F32 GM093550/GM/NIGMS NIH HHS; P30 DK072437/DK/NIDDK NIH HHS; P30 ES003819/ES/NIEHS NIH HHS; P30 ES003819/ES/NIEHS NIH HHS; R01 ES008996/ES/NIEHS NIH HHS; R01 ES008996-15/ES/NIEHS NIH HHS; R01 ES08996/ES/NIEHS NIH HHS; T32 ES07141/ES/NIEHS NIH HHS
Chemical
Reg. No./Substance:
0/Fatty Acids; 0/Sterols; 7440-48-4/Cobalt
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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