Department of Obstetrics and Gynecology, The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, Anhui 230001, China.
Department of Anesthesiology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, China.
Oxid Med Cell Longev. 2020 Jul 29;2020:2405135. doi: 10.1155/2020/2405135. eCollection 2020.
. 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.
. 先前的研究表明，过氧化物酶 1（Prdx1）是生理和病理心血管事件的重要调节剂。本研究旨在探讨 Prdx1 在阿霉素（DOX）诱导的心脏毒性中的作用和潜在机制。在小鼠中诱导心脏特异性表达 Prdx1，然后给予小鼠单次 DOX（15mg/kg）注射以产生心脏毒性。首先，我们的研究表明，DOX 处理后心脏和心肌细胞中 Prdx1 的表达上调。其次，我们提供了直接证据表明 Prdx1 过表达通过减轻氧化应激和心肌细胞凋亡来改善 DOX 诱导的心脏毒性。机制上，我们发现 DOX 处理增加了心脏和心肌细胞中凋亡信号调节激酶 1（ASK1）和下游蛋白 p38 的磷酸化水平，而过表达 Prdx1 则降低了这些效应。相反，抑制 Prdx1 通过 ASK1/p38 通路促进 DOX 诱导的心脏损伤。这些结果表明，Prdx1 可能是预防 DOX 诱导的心脏毒性的有效治疗选择。
