瘦蛋白(leptin)介导的腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号转导途径在脂肪代谢的调节中起重要作用。瘦蛋白与其受体结合使AMPK信号转导途径激活,最终激活肉碱脂酰转移酶-1,通过促进脂肪酸氧化而参与脂肪代谢的...瘦蛋白(leptin)介导的腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号转导途径在脂肪代谢的调节中起重要作用。瘦蛋白与其受体结合使AMPK信号转导途径激活,最终激活肉碱脂酰转移酶-1,通过促进脂肪酸氧化而参与脂肪代谢的调节。本文主要介绍近年来关于瘦蛋白介导的AMPK信号转导途径的组成、活性调节及其作用机制的最新研究进展。展开更多
AIM:Coptidis Rhizoma(CR),the dried rhizomes of Asian herbs(including Coptis chinensis Franch),has been used to treat diabetes mellitus for thousands of years.We explored the possibility that CR acts directly on skelet...AIM:Coptidis Rhizoma(CR),the dried rhizomes of Asian herbs(including Coptis chinensis Franch),has been used to treat diabetes mellitus for thousands of years.We explored the possibility that CR acts directly on skeletal muscle,the major organ responsible for glucose homeostasis,and activates 5'-AMP-activated protein kinase(AMPK),a signaling intermediary leading to metabolic enhancement of skeletal muscle.METHODS:Isolated rat epitrochlearis and soleus muscles were incubated in a buffer containing a CR water extract(CE),and activation of AMPK and related events were examined.RESULTS:In response to CE treat-ment,phosphorylation of Thr172 at the catalyticαsubunit of AMPK,an essential step for full kinase activation,increased in both mus-cles.Phosphorylation of Ser79 of acetyl CoA carboxylase(ACC),an endogenous substrate of AMPK,increased concomitantly.Analysis of isoform-specific AMPK activity revealed that CE activated both the α1 and α2 isoforms of the catalytic subunit.Importantly,the maximal effect of CE on AMPK phosphorylation was significantly greater than that of berberine(BBR),indicating that the action of CE is not totally ascribed to BBR.CONCLUSION:We propose that CE is an acute activator of AMPK in both fast-and slow-twitch skeletal muscles.展开更多
Mitochondrial dysfunction is implicated in Alzheimer’s disease (AD) and disruption of mitochondrial dynamic pathways has been documented in brains from patients diagnosed with AD;although it is unclear whether other ...Mitochondrial dysfunction is implicated in Alzheimer’s disease (AD) and disruption of mitochondrial dynamic pathways has been documented in brains from patients diagnosed with AD;although it is unclear whether other tissues are also affected. Much less is known about the mitochondria in patients diagnosed with sporadic Inclusion Body Myositis (sIBM). The current study examined mitochondrial biology in skeletal muscle from AD and sIBM patients compared to healthy, elderly individuals. Skeletal muscle samples were obtained from the National Disease Research Interchange and mRNA, protein content, and enzyme activity was used to assess mitochondrial parameters. Patients diagnosed with AD or sIBM demonstrated reduced mitofusin 2 and optic atrophy protein 1 protein. AD patients also displayed increased mRNA of superoxide dismutase 2, catalase, and uncoupling protein 3. Amyloid b precursor protein mRNA was higher in sIBM patients only compared to both AD patients and elderly individuals. Both total and phosphorylated AMPK protein content, an upstream regulator of mitochondrial dynamics and biogenesis, were also reduced in sIBM patients. The current study demonstrates a disruption in signaling pathways regulating mitochondrial dynamics in both AD and sIBM patients, although the underlying causes may differ.展开更多
运动导致骨骼肌细胞内的能量平衡状态被破坏,因此,机体恢复与维持能量状态的平衡对运动能力有重要影响,5′-一磷酸腺苷激活的蛋白激酶(5′-AMP activated protein kinase,AMPK)作为细胞内的能量监控器具有这种作用。AMPK在一次性运动中...运动导致骨骼肌细胞内的能量平衡状态被破坏,因此,机体恢复与维持能量状态的平衡对运动能力有重要影响,5′-一磷酸腺苷激活的蛋白激酶(5′-AMP activated protein kinase,AMPK)作为细胞内的能量监控器具有这种作用。AMPK在一次性运动中能以强度和时间依赖性方式激活,其机制主要与运动中AMP/ATP比值改变有关,AMP通过3条途径激活AMPK:直接别构激活;使AMPK成为上游激酶的更适底物;阻遏蛋白磷酸酶对AMPK的抑制,ATP与AMP的作用相拮抗。其他能量状态的变化如磷酸肌酸、肌酸、葡萄糖和肌糖原也对AMPK的激活产生影响。阐明运动激活AMPK的分子机制对理解骨骼肌在运动中的能量代谢具有一定意义。展开更多
文摘瘦蛋白(leptin)介导的腺苷酸激活蛋白激酶(AMP-activated protein kinase,AMPK)信号转导途径在脂肪代谢的调节中起重要作用。瘦蛋白与其受体结合使AMPK信号转导途径激活,最终激活肉碱脂酰转移酶-1,通过促进脂肪酸氧化而参与脂肪代谢的调节。本文主要介绍近年来关于瘦蛋白介导的AMPK信号转导途径的组成、活性调节及其作用机制的最新研究进展。
基金supported by the research grants from the Japan Society for the Promotion of Science (No.20500576)Japan Vascular Disease Research Foundation
文摘AIM:Coptidis Rhizoma(CR),the dried rhizomes of Asian herbs(including Coptis chinensis Franch),has been used to treat diabetes mellitus for thousands of years.We explored the possibility that CR acts directly on skeletal muscle,the major organ responsible for glucose homeostasis,and activates 5'-AMP-activated protein kinase(AMPK),a signaling intermediary leading to metabolic enhancement of skeletal muscle.METHODS:Isolated rat epitrochlearis and soleus muscles were incubated in a buffer containing a CR water extract(CE),and activation of AMPK and related events were examined.RESULTS:In response to CE treat-ment,phosphorylation of Thr172 at the catalyticαsubunit of AMPK,an essential step for full kinase activation,increased in both mus-cles.Phosphorylation of Ser79 of acetyl CoA carboxylase(ACC),an endogenous substrate of AMPK,increased concomitantly.Analysis of isoform-specific AMPK activity revealed that CE activated both the α1 and α2 isoforms of the catalytic subunit.Importantly,the maximal effect of CE on AMPK phosphorylation was significantly greater than that of berberine(BBR),indicating that the action of CE is not totally ascribed to BBR.CONCLUSION:We propose that CE is an acute activator of AMPK in both fast-and slow-twitch skeletal muscles.
文摘Mitochondrial dysfunction is implicated in Alzheimer’s disease (AD) and disruption of mitochondrial dynamic pathways has been documented in brains from patients diagnosed with AD;although it is unclear whether other tissues are also affected. Much less is known about the mitochondria in patients diagnosed with sporadic Inclusion Body Myositis (sIBM). The current study examined mitochondrial biology in skeletal muscle from AD and sIBM patients compared to healthy, elderly individuals. Skeletal muscle samples were obtained from the National Disease Research Interchange and mRNA, protein content, and enzyme activity was used to assess mitochondrial parameters. Patients diagnosed with AD or sIBM demonstrated reduced mitofusin 2 and optic atrophy protein 1 protein. AD patients also displayed increased mRNA of superoxide dismutase 2, catalase, and uncoupling protein 3. Amyloid b precursor protein mRNA was higher in sIBM patients only compared to both AD patients and elderly individuals. Both total and phosphorylated AMPK protein content, an upstream regulator of mitochondrial dynamics and biogenesis, were also reduced in sIBM patients. The current study demonstrates a disruption in signaling pathways regulating mitochondrial dynamics in both AD and sIBM patients, although the underlying causes may differ.
文摘运动导致骨骼肌细胞内的能量平衡状态被破坏,因此,机体恢复与维持能量状态的平衡对运动能力有重要影响,5′-一磷酸腺苷激活的蛋白激酶(5′-AMP activated protein kinase,AMPK)作为细胞内的能量监控器具有这种作用。AMPK在一次性运动中能以强度和时间依赖性方式激活,其机制主要与运动中AMP/ATP比值改变有关,AMP通过3条途径激活AMPK:直接别构激活;使AMPK成为上游激酶的更适底物;阻遏蛋白磷酸酶对AMPK的抑制,ATP与AMP的作用相拮抗。其他能量状态的变化如磷酸肌酸、肌酸、葡萄糖和肌糖原也对AMPK的激活产生影响。阐明运动激活AMPK的分子机制对理解骨骼肌在运动中的能量代谢具有一定意义。
