TY - JOUR
T1 - Anti-apoptotic and anti-inflammatory effects of hydrogen sulfide in a rat model of regional myocardial l/R
AU - Sivarajah, Ahila
AU - Collino, Massimo
AU - Yasin, Mohammed
AU - Benetti, Elisa
AU - Gallicchio, Margherita
AU - Mazzon, Emanuela
AU - Cuzzocrea, Salvatore
AU - Fantozzi, Roberto
AU - Thiemermann, Christoph
PY - 2009/3
Y1 - 2009/3
N2 - Hydrogen sulfide (H 2S) is a novel gaseous mediator produced by cystathionine-β-synthase and cystathionines-α-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H 2S 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 mech-anism(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 l/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial l/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 l/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-kb, (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 l/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.
AB - Hydrogen sulfide (H 2S) is a novel gaseous mediator produced by cystathionine-β-synthase and cystathionines-α-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H 2S 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 mech-anism(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 l/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial l/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 l/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-kb, (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 l/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.
KW - Apoptosis
KW - Hydrogen sulfide
KW - Infarct size
KW - Inflammation and regional myocardial infarction
UR - http://www.scopus.com/inward/record.url?scp=62449302475&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=62449302475&partnerID=8YFLogxK
U2 - 10.1097/SHK.0b013e318180ff89
DO - 10.1097/SHK.0b013e318180ff89
M3 - Article
C2 - 18636044
AN - SCOPUS:62449302475
VL - 31
SP - 267
EP - 274
JO - Shock
JF - Shock
SN - 1073-2322
IS - 3
ER -