| 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: 2013-01-28 |
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. |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: Iridoid glycosides fraction of Folium syringae leaves modulates NF-?B signal pathway and intestinal ...
Next Document: Environmental levels of the antiviral oseltamivir induce development of resistance mutation H274Y in...