Peroxiredoxin-1 Overexpression Attenuates Doxorubicin-Induced Cardiotoxicity by Inhibiting Oxidative Stress and Cardiomyocyte Apoptosis

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.

Palmatine Protects against Cerebral Ischemia/Reperfusion Injury by Activation of the AMPK/Nrf2 Pathway

“…Thus, it can be speculated that PAL could decrease oxidative DNA damage during cerebral I/R injury. SOD catalyzes the conversion of superoxide anion radicals to hydrogen peroxide, and the latter is further reduced into molecular oxygen and water by CAT [35,36]. As a product of lipid peroxidation, MDA has been used to assess free radical levels in cerebral I/R injury [37].…”

Cullin-5 neddylation-mediated NOXA degradation is enhanced by PRDX1 oligomers in colorectal cancer

“…However, to date, whether ubiquitination pathway associated with NOXA degradation was simultaneously altered under oxidative stress conditions and how is this coordinated have been rarely reported. PRDX1, known as one member of peroxiredoxin family, has been demonstrated to have tumor-promoting 29 – 31 and apoptosis-inhibiting 45 – 47 role in several types of cancer. In this research, we found that PRDX1 staining was significantly higher in CRC tissues than in ANTs and that PRDX1 can inhibit cancer cell apoptosis by decreasing NOXA levels.…”

1‐O‐Hexyl‐2,3,5‐Trimethylhydroquinone Ameliorates the Development of Preeclampsia through Suppression of Oxidative Stress and Endothelial Cell Apoptosis

“…Excessive ROS can induce placental dysfunction by suppression of placental angiogenesis, induction endothelial damage, and immune malfunction, which are suggested to be the underlie of PE development [ 11 ] [ 30 ],. In order to maintain cellular redox homeostasis, cells are equipped with antioxidant enzymes or nonenzymatic antioxidants, including SOD, CAT, and GSH, which can scavenge ROS and inhibit free radical formation [ 31 , 32 ]. Previous study demonstrated that the levels of SOD, CAT, and GSH were significantly lower in women with PE than in healthy women, suggesting that the antioxidant protective capacity was decreased in women with preeclampsia [ 33 – 35 ].…”