Recent studies have revealed that proper exercise can reduce the risk of chronic disease and is beneficial to the body. Peptides have been shown to play an important role in various pathological processes, including cardiovascular diseases. However, little is known about the role of exercise-induced peptides in cardiovascular disease. We aimed to explore the function and mechanism of TAG-23 peptide in reperfusion injury and oxidative stress. Treatment with TAG-23 peptide significantly improved cell viability, the mitochondrial membrane potential, and ROS levels and reduced LDH release, the apoptosis rate and caspase 3 activation in vitro. In vivo, TAG-23 ameliorated MI and heart failure induced by I/R or DOX treatment. Pull-down assays showed that TAG-23 can bind to PKG . The TAG-23-PKG complex inhibited PKG degradation through the UPS. We also identified cCbl as the E3 ligase of PKG and found that the interaction between these proteins was impaired by TAG-23 treatment. In addition, we provided evidence that TAG-23 mediated Lys48-linked polyubiquitination and subsequent proteasomal degradation. Our results reveal that a novel exercise-induced peptide, TAG-23, can inhibit PKG degradation by serving as a competitive binding peptide to attenuate the formation of the PKG–cCbl complex. Treatment with TAG-23 may be a new therapeutic approach for reperfusion injury.

最近的研究表明，适当的运动可以降低患慢性病的风险，并且对身体有益。肽已被证明在包括心血管疾病在内的各种病理过程中发挥重要作用。然而，关于运动诱导肽在心血管疾病中的作用知之甚少。我们旨在探讨TAG-23肽在再灌注损伤和氧化应激中的作用和机制。用 TAG-23 肽处理可显着提高细胞活力、线粒体膜电位和 ROS 水平，并降低 LDH 释放、细胞凋亡率和体外 caspase 3 活化。在体内，TAG-23 改善了由 I/R 或 DOX 治疗引起的 MI 和心力衰竭。下拉分析表明 TAG-23 可以与 PKG 结合。TAG-23-PKG 复合物通过 UPS 抑制 PKG 降解。我们还将 cCbl 鉴定为 PKG 的 E3 连接酶，并发现这些蛋白质之间的相互作用因 TAG-23 处理而受损。此外，我们提供了 TAG-23 介导 Lys48 连接的多泛素化和随后的蛋白酶体降解的证据。我们的研究结果表明，一种新的运动诱导肽 TAG-23 可以通过作为竞争性结合肽来抑制 PKG 降解，从而减弱 PKG-cCbl 复合物的形成。用 TAG-23 治疗可能是再灌注损伤的一种新的治疗方法。可以通过作为竞争性结合肽抑制 PKG 降解来减弱 PKG-cCbl 复合物的形成。用 TAG-23 治疗可能是再灌注损伤的一种新的治疗方法。可以通过作为竞争性结合肽抑制 PKG 降解来减弱 PKG-cCbl 复合物的形成。用 TAG-23 治疗可能是再灌注损伤的一种新的治疗方法。