Expression and protective role of heme oxygenase-1 in delayed myocardial preconditioning.
In the study the authors aimed to demonstrate the expression and protective effect of heme oxygenase-1 (HO-1) in the delayed preconditioning (PC) on cultured myocardiac cells. Neonatal rat cardiac myocytes were exposed to ischemic (ischemic medium [IM] for 20 min) and pharmacological (adenosine, epinephrine, opioid) PC. Twenty-four hours later cells were subjected to a simulated ischemia (SI)--culturing for 3 h in IM, followed by 2-h reperfusion in normal medium--and then lactate dehydrogenase (LDH), live/death ratio, and apoptosis were measured. For demonstrating the protective role of HO-1, its enzymatic activity was competitively inhibited by administration of zinc protoporphyrin IX (ZnPPIX), and HO-1 synthesis was blocked with HO-1 siRNA. Cells in control group were cultured under normoxic conditions. In SI group, cells underwent only an SI without PC. HO-1 expression in all of the groups was demonstrated with immunostaining. Our results showed a significant decrease of LDH release, apoptosis, and cell death in PC groups versus SI group, which has been risen in ZnPPIX- and HO-1 siRNA-treated groups. HO-1 immunostaining showed an appreciable HO-1 expression in PC groups, which was abolished with HO-1 siRNA administration, but not in ZnPPIX group. The results therefore suggest that HO-1 expression increases in both ischemic and pharmacological PC, and HO-1 has cellular protective effect against cell death and apoptosis in ischemia-reperfusion-induced oxidative injury.
Jancsó
Gábor
G
Department of Surgical Research and Techniques, University of Pécs, Medical Faculty, Kodaly Zoltan St. 20, Pécs, H-7624 Hungary. jancsogabor@hotmail.com
Cserepes
Barbara
B
Gasz
Balázs
B
Benkó
László
L
Borsiczky
Balázs
B
Ferenc
Andrea
A
Kürthy
Mária
M
Rácz
Boglárka
B
Lantos
János
J
Gál
János
J
Arató
Endre
E
Sínayc
Lószló
L
Wéber
György
G
Róth
Erzsébet
E
D000818:Animals; D000831:Animals, Newborn; D002478:Cells, Cultured; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics / Q000502:physiology; D019157:Ischemic Preconditioning, Myocardial; D009206:Myocardium / Q000166:cytology / Q000201:enzymology*; D051381:Rats; D017208:Rats, Wistar
D051547:Heme Oxygenase-1