Document Detail


NADPH oxidases as a source of oxidative stress and molecular target in ischemia/reperfusion injury.
MedLine Citation:
PMID:  23090009     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Ischemia/reperfusion injury (IRI) is crucial in the pathology of major cardiovascular diseases, such as stroke and myocardial infarction. Paradoxically, both the lack of oxygen during ischemia and the replenishment of oxygen during reperfusion can cause tissue injury. Clinical outcome is also determined by a third, post-reperfusion phase characterized by tissue remodeling and adaptation. Increased levels of reactive oxygen species (ROS) have been suggested to be key players in all three phases. As a second paradox, ROS seem to play a double-edged role in IRI, with both detrimental and beneficial effects. These Janus-faced effects of ROS may be linked to the different sources of ROS or to the different types of ROS that exist and may also depend on the phase of IRI. With respect to therapeutic implications, an untargeted application of antioxidants may not differentiate between detrimental and beneficial ROS, which might explain why this approach is clinically ineffective in lowering cardiovascular mortality. Under some conditions, antioxidants even appear to be harmful. In this review, we discuss recent breakthroughs regarding a more targeted and promising approach to therapeutically modulate ROS in IRI. We will focus on NADPH oxidases and their catalytic subunits, NOX, as they represent the only known enzyme family with the sole function to produce ROS. Similar to ROS, NADPH oxidases may play a dual role as different NOX isoforms may mediate detrimental or protective processes. Unraveling the precise sequence of events, i.e., determining which role the individual NOX isoforms play in the various phases of IRI, may provide the crucial molecular and mechanistic understanding to finally effectively target oxidative stress.
Authors:
Pamela W M Kleikers; K Wingler; J J R Hermans; I Diebold; S Altenhöfer; K A Radermacher; B Janssen; A Görlach; H H H W Schmidt
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-10-23
Journal Detail:
Title:  Journal of molecular medicine (Berlin, Germany)     Volume:  -     ISSN:  1432-1440     ISO Abbreviation:  J. Mol. Med.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-23     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9504370     Medline TA:  J Mol Med (Berl)     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Affiliation:
Vascular Drug Discovery Group (VDDG), Department of Pharmacology and Cardiovascular Research Institute Maastricht (CARIM), Faculty of Health, Medicine and Life Sciences, Maastricht University, Universiteitssingel 50, 6229 ER, Maastricht, The Netherlands, p.kleikers@maastrichtuniversity.nl.
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