MnSOD in mouse heart: acute responses to ischemic preconditioning and ischemia-reperfusion injury.
Manganese superoxide dismutase (MnSOD) is one of the main antioxidant enzymes that protects the heart against ischemia-reperfusion (I/R) injury. Ischemic preconditioning (IPC) is a short period of ischemia-reperfusion that reduces subsequent prolonged I/R injury. Although MnSOD localizes in mitochondria, the immediate subcellular distribution of MnSOD in heart after IPC and I/R has not been studied. In a Langendorff mouse heart model, IPC significantly improved cardiac function and reduced the infarction size induced by I/R. Immunoblotting and double immunostaining in fresh preparations revealed that I/R resulted in an increase in cytosolic MnSOD content accompanied by the release of cytochrome c. In contrast, IPC increased mitochondrial MnSOD and reduced cytosolic MnSOD and cytochrome c release induced by I/R. We found that compared with freshly prepared fractions, the freeze-thaw approach results in mitochondrial integrity disruption and release of large amounts of MnSOD into the cytosol along with mitochondrial markers even in the absence of I/R. In contrast, fresh preparations exhibit early MnSOD release into the cytosol after I/R that is prevented by IPC and cyclosporin A administration.
Jin
Zhu-Qiu
ZQ
Cardiology Section (111C 4150 Clement St., San Francisco, CA 94121, USA. Joel.Karliner@med.va.gov
Zhou
Hui-Zhong
HZ
Cecchini
Gary
G
Gray
Mary O
MO
Karliner
Joel S
JS
D000818:Animals; D016572:Cyclosporine / Q000627:therapeutic use; D003600:Cytosol / Q000201:enzymology; D005615:Freezing; D066298:In Vitro Techniques; D019157:Ischemic Preconditioning, Myocardial; D051379:Mice; D008929:Mitochondria, Heart / Q000201:enzymology; D015428:Myocardial Reperfusion Injury / Q000201:enzymology* / Q000517:prevention & control; D009206:Myocardium / Q000201:enzymology*; D013482:Superoxide Dismutase / Q000378:metabolism*
D016572:Cyclosporine; D013482:Superoxide Dismutase