Linked Life Data

10569643

Source:http://linkedlifedata.com/resource/pubmed/id/10569643

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9-10
pubmed:dateCreated
1999-12-22
pubmed:abstractText
Poly-ADP-ribose polymerase (PARP) is considered to play an important role in oxidative cell damage. We assumed that ischemia-reperfusion resulting from the increasing reactive oxygen species (ROS) can lead to the activation of endogenous mono- and poly-ADP-ribosylation reactions and that the reduction of ROS level by lipoamide, a less known antioxidant, can reverse these unfavorable processes. Experiments were performed on isolated Langendorff hearts subjected to 60-min ischemia followed by reperfusion. ROS, malondialdehyde, deoxyribonucleic acid (DNA) breaks, and NAD+ content were assayed in the hearts, and the ADP-ribosylation of cytoplasmic and nuclear proteins were determined by Western blot assay. Ischemia-reperfusion caused a moderate (30.2 +/- 8%) increase in ROS production determined by the dihydrorhodamine 123 method and significantly increased the malondialdehyde production (from < 1 to 23 +/- 2.7 nmol/ml), DNA damage (undamaged DNA decreased from 71 +/- 7% to 23.1 +/- 5%), and NAD+ catabolism. In addition, ischemia-reperfusion activated the mono-ADP-ribosylation of GRP78 and the self-ADP-ribosylation of the nuclear PARP. The perfusion of hearts with lipoamide significantly decreased the ischemia-reperfusion-induced cell membrane damage determined by enzyme release (LDH, CK, and GOT), decreased the ROS production, reduced the malondialdehyde production to 5.5 +/- 2.4 nmol/ml, abolished DNA damage, and reduced NAD+ catabolism. The ischemia-reperfusion-induced activation of poly- and mono-ADP-ribosylation reactions were also reverted by lipoamide. In isolated rat heart mitochondria, dihydrolipoamide was found to be a better antioxidant than dihydrolipoic acid. Ischemia-reperfusion by ROS overproduction and increasing DNA breaks activates PARP leading to accelerated NAD+ catabolism, impaired energy metabolism, and cell damage. Lipoamide by reducing ROS levels halts PARP activation and membrane damage and improves the recovery of postischemic myocardium.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0891-5849
pubmed:author
pubmed:issnType
Print
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1103-13
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:10569643-ADP Ribose Transferases, pubmed-meshheading:10569643-Adenosine Diphosphate Ribose, pubmed-meshheading:10569643-Animals, pubmed-meshheading:10569643-Antioxidants, pubmed-meshheading:10569643-DNA Damage, pubmed-meshheading:10569643-Enzyme Activation, pubmed-meshheading:10569643-Lipid Peroxidation, pubmed-meshheading:10569643-Male, pubmed-meshheading:10569643-Mitochondria, Heart, pubmed-meshheading:10569643-Myocardial Reperfusion Injury, pubmed-meshheading:10569643-NAD, pubmed-meshheading:10569643-Perfusion, pubmed-meshheading:10569643-Poly(ADP-ribose) Polymerases, pubmed-meshheading:10569643-Proteins, pubmed-meshheading:10569643-Rats, pubmed-meshheading:10569643-Rats, Wistar, pubmed-meshheading:10569643-Reactive Oxygen Species, pubmed-meshheading:10569643-Thioctic Acid
pubmed:year
1999
pubmed:articleTitle
Enhanced ADP-ribosylation and its diminution by lipoamide after ischemia-reperfusion in perfused rat heart.
pubmed:affiliation
Department of Biochemistry, University Medical School Pecs, Hungary.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't