Document Detail


Electrophilic cyclopentenone isoprostanes in neurodegeneration.
MedLine Citation:
PMID:  17901550     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Although oxidative stress has been implicated in the pathogenesis of numerous neurodegenerative conditions, the precise mechanisms by which reactive oxygen species (ROS) induce neuronal death are still being explored. The generation of reactive lipid peroxidation products is thought to contribute to ROS neurotoxicity. Isoprostanes (IsoPs), prostaglandin-like molecules formed in vivo via the ROS-mediated oxidation of arachidonic acid, have been previously demonstrated to be formed in increased amounts in the brains of patients with various neurodegenerative diseases. Recently, we have identified a new class of IsoPs, known as A(2)- and J(2)-IsoPs or cyclopentenone IsoPs, which are highly reactive electrophiles and form adducts with thiol-containing molecules, including cysteine residues in proteins and glutathione. Cyclopentenone IsoPs are favored products of the IsoP pathway in the brain and are formed abundantly after oxidant injury. These compounds also potently induce neuronal apoptosis by a mechanism which involves glutathione depletion, ROS generation, and activation of several redox-sensitive pathways that overlap with those involved in other forms of oxidative neurodegeneration. Cyclopentenone IsoPs also enhance neurodegeneration caused by other insults at biologically relevant concentrations. These data are reviewed, whereas new data demonstrating the neurotoxicity of J-ring IsoPs and a discussion of the possible role of cyclopentenone IsoPs as contributors to neurodegeneration are presented.
Authors:
Erik S Musiek; Bethann McLaughlin; Jason D Morrow
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't; Review    
Journal Detail:
Title:  Journal of molecular neuroscience : MN     Volume:  33     ISSN:  0895-8696     ISO Abbreviation:  J. Mol. Neurosci.     Publication Date:  2007 Sep 
Date Detail:
Created Date:  2007-09-28     Completed Date:  2008-03-04     Revised Date:  2013-06-06    
Medline Journal Info:
Nlm Unique ID:  9002991     Medline TA:  J Mol Neurosci     Country:  United States    
Other Details:
Languages:  eng     Pagination:  80-6     Citation Subset:  IM    
Affiliation:
Division of Clinical Pharmacology, Department of Medicine, Vanderbilt University School of Medicine, 526 RRB, 23rd and Pierce Aves, Nashville, TN 37232-6602, USA.
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / physiology
Brain / metabolism
Cyclopentanes / chemistry*,  metabolism
Isoprostanes / chemistry*,  metabolism
Molecular Structure
Neurodegenerative Diseases / metabolism*
Oxidation-Reduction
Oxidative Stress
Reactive Oxygen Species / metabolism
Grant Support
ID/Acronym/Agency:
CA77839/CA/NCI NIH HHS; DK48831/DK/NIDDK NIH HHS; ES13125/ES/NIEHS NIH HHS; GM15431/GM/NIGMS NIH HHS; HD15052/HD/NICHD NIH HHS; NS050396/NS/NINDS NIH HHS; R01 NS050396-04/NS/NINDS NIH HHS; RR00095/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Cyclopentanes; 0/Isoprostanes; 0/Reactive Oxygen Species; Q0U2IGF9CK/cyclopentenone
Comments/Corrections

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