The peptide from C- Phycocyanin alleviates myocardial ischemia-reperfusion injury by suppressing ferroptosis via upregulating UCHL3

作者：Zhaoqing Li, Ruolan Chen, Luning Qin, Xiaojian Xu, Xuezhe Wang, Guoliang Zhang, Zhijun Liu, Banghui Wang, Bing Li, Xian‐Ming Chu · 发表于：Free Radical Biology and Medicine · 年份：2025 · DOI：10.1016/j.freeradbiomed.2025.05.419 · 被引用次数：8 · 研究领域：Ferroptosis and cancer prognosis、MicroRNA in disease regulation、Circular RNAs in diseases

Myocardial ischemia-reperfusion injury (MIRI) constitutes an essential hurdle following reperfusion therapy for acute myocardial infarction (AMI), which the mechanism involves oxidative stress, inflammatory response, calcium overload, and ferroptosis, etc. MAQAAEYYR (P2), a kind of marine-derived bioactive peptide from C-Phycocyanin (C-PC), exhibits remarkable antioxidant properties. Due to its low molecular weight, P2 exhibits superior bioavailability compared to C-PC. A previous study has confirmed that C-PC could alleviate ischemia-reperfusion (I/R)-induced cardiac dysfunction. However, whether the peptide derived from C-PC has the potential to protect the heart against ischemia-reperfusion injury deserves consideration and investigation. In this study, C57BL/6 male mice and H9C2 cardiomyocytes were used to construct myocardial ischemia-reperfusion (MI/R) and oxygen-glucose deprivation/reoxygenation (OGD/R) injury models in vivo and in vitro respectively. We demonstrated that P2 significantly improved myocardial function, myocardial enzymes, myocardial fibrosis, and mitochondrial ultrastructure, while mitigating oxidative stress damage and ferroptosis caused by MI/R. In vitro, P2 markedly enhanced cell viability, suppressed the generation of reactive oxygen species (ROS) and malondialdehyde (MDA), elevated glutathione (GSH) and superoxide dismutase (SOD) levels, and prevented the occurrence of ferroptosis. Furthermore, we revealed that ubiquitin carboxyl terminal hydrolase...