To date, there have been no reports regarding the role of TAG-23 peptide in cardiovascular disease. Transgelin, which is an androgen receptor (AR) inhibitor, can suppress AR function in LNCaP cells by binding with p53. Transgelin knockout mice show decreased actin content. TAG-23 peptide is derived from transgelin, which is primarily expressed in smooth muscle cells. A wound healing assay showed that compared with a scramble peptide, TAG-23 peptide can increase cell migration by affecting the cell cycle and extracellular matrix remodeling. Live-cell microscopy was utilized to observe the effect of TAG-23 on migration. In the peptidome, the endogenous peptide TAG-23 attracted our attention because it is upregulated in the plasma during exercise. Previous studies have quantified peptides that are differentially induced by exercise by 2D-LC–MS/MS, and 5548 unique peptides that are induced at different time points have been screened. Despite advances in the knowledge of cardiovascular diseases, further identification of bioactive peptides will facilitate better understanding of the mechanism of I/R injury. These studies emphasize the importance of peptides in pathological processes. Pretreatment with GLP-1 peptide protects against ischemic cardiac dysfunction and improves heart function during reperfusion. Oral administration of the peptide Val-Pro-Pro, which is derived from casein, reduces proinflammatory macrophage accumulation in adipose tissue. For example, Bβ 15–42 can ameliorate leukocyte transmigration across the endothelial monolayer to ameliorate ischemia–reperfusion (I/R) injury. However, the underlying mechanisms of exercise-induced cardioprotection remain unknown.Īccumulating evidence has shown that peptides play important roles in various pathophysiological processes. These bioactive components may be beneficial for physiological function. Exercise-induced bioactive factors, including peptides, hormones, and nucleic acids, are secreted into the circulatory system and allow cell communication within different organs. Recent studies have shown that the mechanism underlying exercise-induced cardioprotection mainly contributes to increasing antioxidant capacity, anti-inflammatory effects, and the secretion of beneficial hormones or cytokines. Exercise is recommended for patients with heart failure or following MI. It is well established that exercise not only reduces the risks of chronic disease but also provides protection against cardiovascular disease. Cardiomyocyte death resulting from reperfusion injury can be prevented at the end of the ischemic time, and targeting regulated cell death pathways before reperfusion injury appears to be a promising approach to minimize MI injury. Emerging evidence have demonstrated that apoptosis, the inflammatory response, and reactive oxygen species (ROS) are associated with cellular damage during the ischemic period. Myocardial infarction (MI) is the leading cause of death worldwide. Treatment with TAG-23 may be a new therapeutic approach for reperfusion injury. 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. In addition, we provided evidence that TAG-23 mediated Lys48-linked polyubiquitination and subsequent proteasomal degradation. We also identified cCbl as the E3 ligase of PKG and found that the interaction between these proteins was impaired by TAG-23 treatment. The TAG-23-PKG complex inhibited PKG degradation through the UPS. Pull-down assays showed that TAG-23 can bind to PKG. In vivo, TAG-23 ameliorated MI and heart failure induced by I/R or DOX treatment. 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. We aimed to explore the function and mechanism of TAG-23 peptide in reperfusion injury and oxidative stress. However, little is known about the role of exercise-induced peptides in cardiovascular disease. Peptides have been shown to play an important role in various pathological processes, including cardiovascular diseases. Recent studies have revealed that proper exercise can reduce the risk of chronic disease and is beneficial to the body.
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