Wang Xuejun, Zhang Li, Feng Mengwen, Xu Zhongqing, Cheng Zijie, Qian Lingmei
Hongqiao International Institute of Medicine, Tongren Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Department of Cardiology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China.
Front Pharmacol. 2022 Sep 8;13:873614. doi: 10.3389/fphar.2022.873614. eCollection 2022.
Increasing evidence revealed that apoptosis and oxidative stress injury were associated with the pathophysiology of doxorubicin (DOX)-induced myocardial injury. ELABELA (ELA) is a newly identified peptide with 32 amino acids, can reduce hypertension with exogenous infusion. However, the effect of 11-residue furn-cleaved fragment (ELA-11) is still unclear. We first administrated ELA-11 in DOX-injured mice and measured the cardiac function and investigated the effect of ELA-11 . We found that ELA-11 alleviated heart injury induced by DOX and inhibited cardiac tissues from apoptosis. , ELA-11 regulated the sensitivity towards apoptosis induced by oxidative stress with DOX treatment through PI3K/AKT and ERK/MAPK signaling pathway. Similarly, ELA-11 inhibited oxidative stress-induced apoptosis in cobalt chloride (CoCl)-injured cardiomyocytes. Moreover, ELA-11 protected cardiomyocyte by interacting with Apelin receptor (APJ) by using 4-oxo-6-((pyrimidin-2-ylthio) methyl)-4H-pyran-3-yl 4-nitrobenzoate (ML221). Hence, our results indicated a protective role of ELA-11 in oxidative stress-induced apoptosis in DOX-induced myocardial injury.
越来越多的证据表明，细胞凋亡和氧化应激损伤与阿霉素（DOX）诱导的心肌损伤的病理生理学有关。ELABELA（ELA）是一种新发现的由32个氨基酸组成的肽，外源性输注可降低高血压。然而，11个残基的截短片段（ELA-11）的作用仍不清楚。我们首先在DOX损伤的小鼠中给予ELA-11，测量心脏功能并研究ELA-11的作用。我们发现ELA-11减轻了DOX诱导的心脏损伤并抑制了心脏组织的细胞凋亡。此外，ELA-11通过PI3K/AKT和ERK/MAPK信号通路调节DOX处理后氧化应激诱导的细胞凋亡敏感性。同样，ELA-11抑制了氯化钴（CoCl）损伤的心肌细胞中氧化应激诱导的细胞凋亡。此外，ELA-11通过使用4-氧代-6-（（嘧啶-2-基硫代）甲基）-4H-吡喃-3-基4-硝基苯甲酸酯（ML221）与Apelin受体（APJ）相互作用来保护心肌细胞。因此，我们的结果表明ELA-11在DOX诱导的心肌损伤中氧化应激诱导的细胞凋亡中起保护作用。
