Regional Differences in Mitochondrial Anti-oxidant State during Ischemic Preconditioning in Rat Heart
Vu Thi Thu, Dang Van Cuong, Nari Kim, Jae Boum Youm, Mohamad Warda, Won Sun Park, Jae Hong Ko, Euiyong Kim, and Jin Han
Mitochondrial Signaling Laboratory Mitochondria Research Group, Department of Physiology and Biophysics, Cardiovascular and Metabolic Diseases Research Center, Biohealth Products Research Center, Inje University College of Medicine, Busan 614-735, Korea
Ischemic preconditioning (IPC) is known to protect the heart against ischemia/reperfusion (IR)-induced injuries, and regional differences in the mitochondrial antioxidant state during IR or IPC may promote the death or survival of viable and infarcted cardiac tissues under oxidative stress. To date, however, the interplay between the mitochondrial antioxidant enzyme system and the level of reactive oxygen species (ROS) in the body has not yet been resolved. In the present study, we examined the effects of IR- and IPC-induced oxidative stresses on mitochondrial function in viable and infarcted cardiac tissues. Our results showed that the mitochondria from viable areas in the IR-induced group were swollen and fused, whereas those in the infarcted area were heavily damaged. IPC protected the mitochondria, thus reducing cardiac injury. We also found that the activity of the mitochondrial antioxidant enzyme system, which includes manganese superoxide dismutase (Mn-SOD), was enhanced in the viable areas compared to the infarcted areas in proportion with decreasing levels of ROS and mitochondrial DNA (mtDNA) damage. These changes were also present between the IPC and IR groups. Regional differences in Mn-SOD expression were shown to be related to a reduction in mtDNA damage as well as to the release of mitochondrial cytochrome c (Cyt c). To the best of our knowledge, this might be the first study to explore the regional mitochondrial changes during IPC. The present findings are expected to help elucidate the molecular mechanism involved in IPC and helpful in the development of new clinical strategies against ischemic heart disease.
Keywords: DNA damage, Ischemic preconditioning, Mitochondria, Oxidative stress, Superoxide