Carbon monoxide-releasing molecule CORM-2 protects against renal ischemia-reperfusion injury in mice by decrease HMGB1 nucleocytoplasmic shuttling

Abstract

Objective To examine the relationship between the the protective effect of CORM-2 and translocation of HMGB1 in murine renal ischemia-reperfusion injury. Methods In the ischemia-reperfusion injury of mice, the translocation of HMGB1 after 50 minutes renal ischemia was evaluated. CORM-2 was administered 1 h before ischemia. Immunohistochemistry and Western blot were performed to examine the relationship between CORM-2 and HMGB1 nucleocytoplasmic shuttling in the murine renal ischemia-reperfusion injury. Results We found that HMGB1 released from the renal epithelium nucleus into cytoplasm significantly increased after renal ischemia. In contrast, CORM-2 pretreated significantly decreased the HMGB1 level in renal tubular epitheliums cytoplasm. Immunohistochemistry and Western blot were showed that amount of HMGB1 translocated from nucleus to cytoplasm in murine renal ischemia-reperfusion injury, whereas, pretreatment of CORM-2 significantly inhibited HMGB1 nucleocytoplasmic shuttling. Conclusions CORM-2 inhibits renal epithelium releasing HMGB1, an early mediator of inflammation, to attenuate the renal I/R injury in mice. Key words: Reperfusion Injury; Kidney; Carbon Monoxide; Nuclear Proteins