Visit our Expo - Redox and Inflammation signaling 2012

Session XVII : Cell signaling in health and disease Poster XVII, 24
Expression and protective role of heme oxygenase-1 in the delayed myocardial
preconditioning
Gabor Jancso, Barbara Cserepes, Balazs Borsiczky, Andrea Ferenc, Boglarka Racz,
Janos Lantos, E Roth
Department of Surgical Research and Techniques, Faculty of Medicine, University of
Pécs, Pécs, Hungary ; e-mail: jancsogabor@hotmail.com
Ischaemic preconditioning (PC) is an endogenous adaptation response of the myocardium to
stress, whereby short ischaemic-reperfusion periods increase the myocardium’s tolerance to a
longer ischaemic attack. Heme oxygenase (HO)-1, that degrades the pro-oxidant heme to
carbon monoxide and to the antioxidant bilirubin, has been shown to protect cardiomyocytes
against oxidative injury. We aimed to demonstrate the expression and protective effect of HO-
1 in the delayed PC. Neonatal rat cardiac myocytes were exposed to ischaemic PC (ischaemic
medium for 20 min) and pharmacological (adenosine, norepinephrine, opioid)
preconditioning (group 1). 24 hours later cells were subjected to a test ischaemia (TI) –
culturing for 3 hours in ischaemic medium, following with a 2 h reperfusion in normal
medium – and then lactate dehydrogenase (LDH), live/death ratio, and apoptosis were
measured. In group 2. HO-1 enzymatic activity was competitively inhibited by administration
of zinc protoporphyrin (ZnPPIX) after PC. In group 3. HO-1 synthesis was blocked with HO-
1 siRNA before PC. In group 4. HO-1 expression was induced by administration of cobalt
protoporphyrin (CoPPIX). In the group 5. (control) we made only test ischaemia without
preconditioning. Furthermore we demonstrated HO-1 expression in the various groups with
immuno-staining. Our results showed a significant decrease of LDH release in PC groups vs.
control group, that has been risen in ZnPPIX and HO-1 siRNA treated groups. Increased
apoptosis and cell death were seen in PC groups which were treated with ZnPPIX and HO-1
siRNA. CoPPIX pretreatment resulted in decreased LDH level, apoptosis and cell death,
which was comparable to PC groups. HO-1 immuno-staining showed an appreciable HO-1
expression in PC groups, which was abolished with HO-1 siRNA administration, but not in
ZnPPIX group. Our results suggest that HO-1 expression increases in both ischaemic and
pharmacological PC, and HO-1 has cellular protective effect against cell death and apoptosis
in ischaemia-reperfusion induced oxidative injury. Supported by OTKA T-048851; OTKA
F046593; OTKA F046504; OTKA T 038035.
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