RGD Reference Report - ANTIAPOPTOTIC AND ANTI-INFLAMMATORY EFFECTS OF HYDROGEN SULFIDE IN A RAT MODEL OF REGIONAL MYOCARDIAL I/R. - Rat Genome Database

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ANTIAPOPTOTIC AND ANTI-INFLAMMATORY EFFECTS OF HYDROGEN SULFIDE IN A RAT MODEL OF REGIONAL MYOCARDIAL I/R.

Authors: Sivarajah, A  Collino, M  Yasin, M  Benetti, E  Gallicchio, M  Mazzon, E  Cuzzocrea, S  Fantozzi, R  Thiemermann, C 
Citation: Sivarajah A, etal., Shock. 2008 Jul 16.
RGD ID: 2298773
Pubmed: PMID:18636044   (View Abstract at PubMed)
DOI: DOI:10.1097/SHK.0b013e318180ff89   (Journal Full-text)

Hydrogen sulfide (H2S) is a novel gaseous mediator produced by cystathionine-beta-synthase and cystathionine-gamma-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial I/R, we investigated the effects of an H2S donor (sodium hydrogen sulfide [NaHS]) on the infarct size and apoptosis caused by ischemia (25 min) and reperfusion (2 h). Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by NaHS. Specifically, we demonstrate that NaHS (1) attenuates the increase in caspase 9 activity observed in cardiac myocytes isolated from the area at risk (AAR) of hearts subjected in vivo to regional myocardial I/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial I/R. The cardioprotective effects of NaHS were abolished by 5-hydroxydeconoate, a putative mitochondrial adenosine triphosphate-sensitive potassium channel blocker. Furthermore, NaHS attenuated the increase in the I/R-induced (1) phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase, (2) translocation from the cytosol to the nucleus of the p65 subunit of nuclear factor-kappaB, (3) intercellular adhesion molecule 1 expression, (4) polymorphonuclear leukocyte accumulation, (5) myeloperoxidase activity, (6) malondialdehyde levels, and (7) nitrotyrosine staining determined in the AAR obtained from rat hearts subjected to regional myocardial I/R. In conclusion, we demonstrate that the cardioprotective effect of NaHS is secondary to a combination of antiapoptotic and anti-inflammatory effects. The antiapoptotic effect of NaHS may be in part due to the opening of the putative mitochondrial adenosine triphosphate-sensitive potassium channels.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Myocardial Reperfusion Injury  ISORela (Rattus norvegicus)2298773; 2298773protein:altered localization:nucleusRGD 
Myocardial Reperfusion Injury  IDA 2298773protein:altered localization:nucleusRGD 

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
response to inorganic substance  IEP 2298773 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Rela  (RELA proto-oncogene, NF-kB subunit)

Genes (Mus musculus)
Rela  (v-rel reticuloendotheliosis viral oncogene homolog A (avian))

Genes (Homo sapiens)
RELA  (RELA proto-oncogene, NF-kB subunit)


Additional Information