Identification of a novel native peptide derived from 60S ribosomal protein L23a that translationally regulates p53 to reduce myocardial ischemia-reperfusion. (January 2022)

• Record Type: Journal Article
• Authors: Yin, Anwen; Feng, Mengwen; Zhang, Li; Cheng, Zijie; Li, Yun; Qian, Lingmei
• Is Part Of: Pharmacological research. Volume 175(2022)
• Publication Date: 2022-01
• Subjects: Myocardial ischemia-reperfusion -- Peptide -- P53 -- Translation; Pharmacology -- Periodicals; Pharmacology -- Periodicals; Research -- Periodicals; Médicaments -- Recherche -- Périodiques; Pharmacologie -- Périodiques; 615.105
• DOI: 10.1016/j.phrs.2021.105988
• Languages: English
• ISSNs: 1043-6618

Abstract

Abstract: Myocardial ischemia-reperfusion (I/R) is a severe disease，but its underlying mechanism is not fully elucidated and no effective clinical treatment is available. Utilizing intracellular peptidomics, we identified a novel native peptide PDRL23A (Peptide Derived from RPL23A), that is intimately related to hypoxic stress. We further show that PDRL23A effectively alleviates hypoxia-induced cardiomyocyte injury in vitro, along with improvements in mitochondrial function and redox homeostasis, including ROS accumulation, oxidative phosphorylation, and mitochondrial membrane potential. Strikingly, the in vivo results indicate that, short-term pretreatment with PDRL23A could effectively inhibit I/R-induced cardiomyocyte death, myocardial fibrosis and decreased cardiac function. Interestingly, PDRL23A was found to interact with 60 S ribosomal protein L26 (RPL26), hampering RPL26-governed p53 translation, and resulting in a reduction in the level of p53 protein, which in turn reduced p53-mediated apoptosis under hypoxic conditions. Collectively, a native peptide, PDRL23A, which translationally regulates p53 to protect against myocardial I/R injury, has been identified for the first time. Our findings provide insight into the adaptive mechanisms of hypoxia and present a potential new treatment for myocardial I/R. Graphical Abstract: ga1