Background. Previous research has shown that peroxiredoxin 1 (Prdx1) is an important modulator of physiological and pathophysiological cardiovascular events. This study is aimed at investigating the role and underlying mechanism… Click to show full abstract
Background. Previous research has shown that peroxiredoxin 1 (Prdx1) is an important modulator of physiological and pathophysiological cardiovascular events. This study is aimed at investigating the role and underlying mechanism of Prdx1 in doxorubicin- (DOX-) induced cardiotoxicity. Cardiac-specific expression of Prdx1 was induced in mice, and the mice received a single dose of DOX (15 mg/kg) to generate cardiotoxicity. First, our study demonstrated that Prdx1 expression was upregulated in the heart and in cardiomyocytes after DOX treatment. Second, we provided direct evidence that Prdx1 overexpression ameliorated DOX-induced cardiotoxicity by attenuating oxidative stress and cardiomyocyte apoptosis. Mechanistically, we found that DOX treatment increased the phosphorylation level of apoptosis signal-regulating kinase-1 (ASK1) and the downstream protein p38 in the heart and in cardiomyocytes, and these effects were decreased by Prdx1 overexpression. In contrast, inhibiting Prdx1 promoted DOX-induced cardiac injury via the ASK1/p38 pathway. These results suggest that Prdx1 may be an effective therapeutic option to prevent DOX-induced cardiotoxicity.
               
Click one of the above tabs to view related content.