RESUMEN
Adaptation of cardiac muscle to regular exercise results in morphological and structural changes known as physiological cardiac hypertrophy, to which the Hippo signaling pathway might have contributed. Two major terminal effectors in the Hippo signaling pathway are Yes-associated protein (YAP) and its homolog transcriptional coactivator with PDZ-binding motif (TAZ). The latest studies have reported the role of YAP and TAZ in different life stages, such as in fetal, neonatal, and adult hearts. Their regulation might involve several mechanisms and effectors. One of the possible coregulators is exercise. Exercise plays a role in cardiomyocyte hypertrophic changes during different stages of life, including in aged hearts. YAP/TAZ signaling pathway has a role in physiological cardiac hypertrophy induced by exercise and is associated with cardiac remodelling. Thus, it can be believed that exercise has roles in activating the signaling pathway of YAP and TAZ in aged cardiomyocytes. However, the studies regarding the roles of YAP and TAZ during cardiomyocyte aging are limited. The primary purpose of this review is to explore the response of cardiovascular aging to exercise via signaling pathway of YAP and TAZ.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales , Fosfoproteínas , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Anciano , Envejecimiento , Cardiomegalia , Ejercicio Físico , Humanos , Recién Nacido , Miocitos Cardíacos/metabolismo , Fosfoproteínas/metabolismo , Proteínas Señalizadoras YAPRESUMEN
Yes-associated protein (YAP) is one of the Hippo pathway's two effectors, a pathway associated with organ size control. Research on YAP has focused on its oncogenic potential. However, in cancer cells, aside from inducing growth, YAP was also found to regulate glucose metabolism. The present review explores YAP's control of glucose metabolism and whether these findings are translatable to physiological conditions. According to current literature, YAP induces the transcriptional activity of most genes associated with glucose metabolism from enzymes to transport proteins. In glycolysis and gluconeogenesis, YAP upregulates all enzymes except for enolase and pyruvate kinase. Multiple research has also shown YAP's ability to regulate the expression of glucose transporter of the GLUT family. Additionally, glucose concentration, hypoxia, and hormones such as insulin and glucagon regulate YAP activity and depend on YAP to exert their biological activity. YAP is thus a central regulator of glucose metabolism, controlling both enzymes and proteins involved in glucose transport. YAP is also situated strategically in several pathways controlling glucose and was found to mediate their effects. If these results were consistent in physiological conditions and across glucose-associated metabolic disturbances, then YAP may become a prospective therapeutic target.
Asunto(s)
Glucosa/metabolismo , Péptidos y Proteínas de Señalización Intracelular/metabolismo , Factores de Transcripción/metabolismo , Animales , Gluconeogénesis/genética , Gluconeogénesis/fisiología , Glucólisis/genética , Glucólisis/fisiología , Humanos , Transducción de Señal/genética , Transducción de Señal/fisiologíaRESUMEN
Information about the role of moderate acute treadmill training in modulating autophagy and mitochondrial markers that might be correlated with alteration of muscle fibre gene expression in rat cardiac muscles is very limited. In this present study, the researchers divided twenty male Wistar rats into four groups: sedentary control, 3, 6 and 15 days and subjected them to treadmill training with moderate intensity (20 m/min), 30 min each day. RNA was extracted from cardiac muscles and stored in temperature of -80°C. Specific primers were utilized for semi-quantitative PCR. Treadmill training decreased autophagy-related gene expression (LC3, p62) and upper stream signalling of autophagy (PIK3CA, Akt and mTOR) in 3 and 6 d, but stimulated gene expression of mitochondrial markers (PGC1α, Cox1, Cox2 and Cox4) in 15 days. αMHC gene expression increased while ßMHC gene expression decreased in 15 days. In line with this, autophagy-related genes increased in 3 and 6 days and returned to baseline in 15 days. The increment in mitochondrial gene expression might be correlated with shifting gene expression of αMHC and ßMHC in 15 days. Taken together, acute adaptation in cardiac muscles is stimulated by genetic modulation of autophagy, mitochondrial marker and muscle fibre that may explain physiological cardiac adaptation after training. This study can be used as a reference for optimizing performance in period of cardiac muscle adaptation stimulated by treadmill training.
Asunto(s)
Condicionamiento Físico Animal , Animales , Autofagia , Masculino , Fibras Musculares Esqueléticas , Músculo Esquelético , Miocardio , Ratas , Ratas WistarRESUMEN
Exercise-induced skeletal muscle adaptation requires degradation of cellular components carried out by autophagy. However, the alteration of autophagy by different intensity of exercise in skeletal muscle is still unknown. In the present study, we investigate whether low, moderate, and high-intensity exercises have different impacts on autophagy gene expression in gastrocnemius and soleus muscles of wistar rats. This work is limited because only rats are used, and does not cover human tissues. Twenty male wistar rats were assigned to four groups: sedentary control, low-intensity (LI, 10 m/minute), moderate-intensity (MI, 20 m/minute), and high-intensity (HI, 30 m/minute) exercises. Training was conducted 30 minutes/day with a 5 times/week interval for 8 weeks. RNA and protein were extracted from gastrocnemius and soleus muscles then stored in -80°C. Specific primers and antibodies for autophagy genes and protein levels were utilized for semi-quantitative PCR and Western Blot. Exercises decrease expression of autophagy gene LC3 (LI and MI 0.7 fold, HI 0.8 fold, p < 0.05) in gastrocnemius muscles and soleus muscle (LI, MI, and HI 0.8 fold, p < 0.05) compared to control. On the other side, we observed p62 gene expression decreased in gastrocnemius (0.8 fold, p < 0.05) and soleus (0.9 fold, p < 0.05) muscles with MI, but increased in soleus (1.1 fold, p < 0.05) muscles with HI. This result is consistent with the change of protein level, suggesting that autophagy might be modulated by different type of exercise. This study suggests that intensity of exercise and different type of muscle fibers effect autophagy gene expression in skeletal muscle of wistar rats. MI exercise increases autophagy gene expression in gastrocnemius and soleus muscles, but HI exercise decreases autophagy gene expression in soleus muscles of wistar rats. Soleus muscles are more responsive to exercise compared to gastrocnemius muscles.