Heme oxygenase-1-related carbon monoxide production and ventricular fibrillation in isolated ischemic/reperfused mouse myocardium.
Heme oxygenase-1 (HO-1)-dependent carbon monoxide (CO) production related to reperfusion-induced ventricular fibrillation (VF) was studied in HO-1 wild-type (+/+), heterozygous (+/-), and homozygous (-/-) isolated ischemic/reperfused mouse heart. In HO-1 homozygous myocardium, under aerobic conditions, HO-1 enzyme activity, HO-1 mRNA, and protein expression were not detected in comparison with aerobically perfused wild-type and heterozygous myocardium. In wild-type, HO-1 hetero- and homozygous hearts subjected to 20 min ischemia followed by 2 h of reperfusion, the expression of HO-1 mRNA, protein, and HO-1 enzyme activity was detected in various degrees. A reduction in the expression of HO-1 mRNA, protein, and enzyme activity in fibrillated wild-type and heterozygous myocardium was observed. In reperfused/nonfibrillated wild-type and heterozygous hearts, a reduction in HO-1 mRNA, protein expression, and HO-1 enzyme activity was not observed, indicating that changes in HO-1 mRNA, protein, and enzyme activity could be related to the development of VF. These changes were reflected in the HO-1-related endogenous CO production measured by gas chromatography. In HO-1 knockout ischemic/reperfused myocardium, all hearts showed VF, and no detection in HO-1 mRNA, protein, and enzyme activity was observed. Thus, interventions that are able to increase endogenous CO may prevent the development of VF.
Bak
Istvan
I
Department of Pharmacology, Health and Science Center, University of Debrecen, Nagyerdei krt. 98, 4032-Debrecen, Hungary.
Szendrei
Levente
L
Turoczi
Tibor
T
Papp
Gabor
G
Joo
Ferenc
F
Das
Dipak K
DK
de Leiris
Joel
J
Der
Peter
P
Juhasz
Bela
B
Varga
Edit
E
Bacskay
Ildiko
I
Balla
Jozsef
J
Kovacs
Peter
P
Tosaki
Arpad
A
D000818:Animals; D002248:Carbon Monoxide / Q000378:metabolism*; D006419:Heme Oxygenase (Decyclizing) / Q000032:analysis / Q000378:metabolism* / Q000502:physiology; D051547:Heme Oxygenase-1; D007150:Immunohistochemistry; D008565:Membrane Proteins; D051379:Mice; D018345:Mice, Knockout; D008954:Models, Biological; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000378:metabolism; D009206:Myocardium / Q000737:chemistry / Q000201:enzymology* / Q000378:metabolism; D009924:Organ Culture Techniques; D012333:RNA, Messenger / Q000096:biosynthesis; D014693:Ventricular Fibrillation / Q000201:enzymology / Q000378:metabolism
D008565:Membrane Proteins; D012333:RNA, Messenger; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C496542:Hmox1 protein, mouse