Role of nitrosative stress and activation of poly(ADP-ribose) polymerase-1 in cardiovascular failure associated with septic and hemorrhagic shock
Details
Serval ID
serval:BIB_CAA8D7D9CF1C
Type
Article: article from journal or magazin.
Publication sub-type
Review (review): journal as complete as possible of one specific subject, written based on exhaustive analyses from published work.
Collection
Publications
Institution
Title
Role of nitrosative stress and activation of poly(ADP-ribose) polymerase-1 in cardiovascular failure associated with septic and hemorrhagic shock
Journal
Current Vascular Pharmacology
ISSN
1570-1611 (Print)
Publication state
Published
Issued date
07/2005
Volume
3
Number
3
Pages
293-9
Notes
Journal Article
Research Support, Non-U.S. Gov't
Review --- Old month value: Jul
Research Support, Non-U.S. Gov't
Review --- Old month value: Jul
Abstract
Reactive oxygen and nitrogen species, particularly peroxynitrite, are potent inducers of tissue damage during systemic inflammatory response and circulatory shock. Recent evidence indicates that the toxicity of these species largely depends on their ability to trigger activation of the nuclear enzyme poly(adenosine 5'-diphosphate ribose) polymerase-1 (PARP-1). Following excessive activation, PARP-1 depletes the intracellular stores of its substrate, nicotinamide adenine dinucleotide, thus slowing glycolysis, generation of high energy phosphates, and mitochondrial electron transport. Consequently, the severe metabolic crisis induced by PARP-1 activation results in acute cell dysfunction and necrotic cell death. In addition, activation of PARP-1 plays an important role in the upregulation of inflammatory cascades via a functional association with mitogen-activated protein kinases and several transcription factors, such as nuclear factor kappa B, resulting in augmented expression of pro-inflammatory cytokines, chemokines, adhesion molecules, and enzymes. In severe sepsis and hemorrhage, PARP-1 activation has emerged as one of the central mechanisms of systemic inflammation, endothelial dysfunction, peripheral vascular failure, and reduction of cardiac contractility. Innovative therapeutic strategies based on the pharmacological inhibition of PARP-1 catalytic activity might provide benefits by preventing tissue injury, organ dysfunction, and lethality associated with these conditions.
Keywords
Animals
Anoxia/metabolism
Cardiovascular Diseases/*metabolism
Enzyme Activation
Enzyme Inhibitors/pharmacology
Humans
Inflammation Mediators/metabolism
Poly(ADP-ribose) Polymerases/antagonists & inhibitors/*metabolism
Reactive Nitrogen Species/metabolism
Reactive Oxygen Species/metabolism
Sepsis/metabolism
Shock, Hemorrhagic/metabolism
Signal Transduction
Pubmed
Create date
24/01/2008 18:00
Last modification date
20/08/2019 16:45