The importance of manganese superoxide dismutase in delayed preconditioning: Involvement of reactive oxygen species and cytokines

It is clinically important to elucidate the mechanism underlying the delayed preconditioning against ischomia-reperfusion injury observed 24-72 It after sublethal stress such as brief ischemia, hyperthermia and exercise. The time course of induction of myocardial manganese-superoxide dismutase (Mn-SOD) and appearance of the ischemic tolerance coincide and the percent increase in Mn-SOD activity and percent reduction of infarct size are correlated well under various stresses. Furthermore, treatments with antisense oligodeoxynucleotides to Mn-SOD completely abolished the delayed preconditioning and any increase in Mn-SOD content. These results indicate that Mn-SOD induction plays a pivotal role in the late phase preconditioning afforded with brief ischemia, hyperthermia and exercise. we also showed that cytokines, e.g., tumor necrosis factor-alpha and interleukin- 1 beta, and reactive oxygen species are involved in the process of signal transduction for the Mn-SOD induction. (C) 2002 Elsevier Science B.V. All rights reserved.