Abstract
An increasing number of studies have associated nuclear factor-κB (NF-κB) activation to the progression of myocardial infarction (MI). Multiple members of the ubiquitin-specific protease (USP) family regulate the NF-κB signaling pathway. This study attempted to investigate the function and underlying mechanism of USP family members in MI. Monocytes were isolated from peripheral blood samples of MI and healthy control, and the expression of several USP family members and NF-κB was examined. After USP47 knockdown or overexpression, cell apoptosis, related protein levels, and NF-κB promoter activity were measured. We found that USP47 and NF-κB expression was significantly increased in MI, and USP47 was positively correlated with NF-κB. In a rat H9c2 myocardial cell ischemia/reperfusion (I/R) injury model, USP47 expression was increased in a time-dependent manner. USP47 knockdown decreased I/R injury-induced apoptosis, with increased survivin and cytoplasmic NF-κB and decreased cleaved caspase-3 and nuclear NF-κB. USP47-induced apoptosis was potently counteracted by the NF-κB inhibitor, and cytoplasmic NF-κB was increased and nuclear NF-κB was decreased. Luciferase reporter showed that USP47 promotes NF-κB promoter activity. These results suggested that USP47 expression may be correlated with MI progression. USP47 knockdown attenuated myocardial cell I/R injury by inhibiting apoptosis.