Aim Stable microtubules （MTs） is involved the mechanism of diabetic cardiomyopathy （DCM）, which is induced by acetylation of α-tubulin. The present study investigated whether SIRT2, a deacetylase, regulates MT st...Aim Stable microtubules （MTs） is involved the mechanism of diabetic cardiomyopathy （DCM）, which is induced by acetylation of α-tubulin. The present study investigated whether SIRT2, a deacetylase, regulates MT stability through α-tubulin deacetylation in DCM and whether the receptor of advanced glycation end products （AGEs） signaling pathway is involved in this effect. Methods Type 1 diabetic mellitus （T1DM） rats model was established by a single intraperitoneal injection of streptozotocin （STZ, 65 mg · kg^-1） , and neonatal rat cardio- myocytes were also cultured. Heart function was detected by Doppler. MT stability was elevated by β-tubulin ex- pression density. The protein expression of SIRT2, acetylated α-tubulin and AGEs receptor were detected by immu- nohistochemistry or Western blots. The interaction of SIRT2 and acetylated α-tubulin was detected by Co-immuno- precipitation. Results In an animal model of T1DM, Western blot and immunohistochemistry revealed downregu- lation of SIRT2 but upregulation of the acetylated α-tubulin protein. These effects were reduced by treatment of aminoguanidine, an inhibitor of AGEs production. HDAC6 expression did not regulated in heart. In primary cul- tures of neonatal rat cardiomyocytes, the AGEs treatment impaired the SIRT2/acetylated α-tubulin signaling path- way, and SIRT2-overexpression reversed the function of AGEs on cardiomyocytes. In addition, gene silencing of AGEs receptor alleviated the impairment effect of AGEs on cardiomyocytes. Conclusion In conclusion, these data demonstrate that AGEs/AGEs receptor promote MT stabilization via the suppression of the SIRT2/acetylated α-tu- bulin signaling pathway in DCM development.展开更多
越来越多的研究表明,晚期糖基化终产物（advanced glycation end products,AGEs）参与了神经系统退行性病变的过程,包括参与了阿尔茨海默病（Alzheimer disease,AD）的发病机制以及β-淀粉样蛋白（Aβ）的沉积,是AD的一个标志性特征。...越来越多的研究表明,晚期糖基化终产物（advanced glycation end products,AGEs）参与了神经系统退行性病变的过程,包括参与了阿尔茨海默病（Alzheimer disease,AD）的发病机制以及β-淀粉样蛋白（Aβ）的沉积,是AD的一个标志性特征。外源性AGEs形成于加热和辐照食品的过程中,展开更多
Endothelial dysfunction,caused by declining impact of endothelium-derived relaxing factors and/or exaggerated production and activity of endothelium-derived contracting factors in the vascular wall,is the common conse...Endothelial dysfunction,caused by declining impact of endothelium-derived relaxing factors and/or exaggerated production and activity of endothelium-derived contracting factors in the vascular wall,is the common consequence of diabetes and hypertension.The degree of endothelial dysfunction predicts future cardiovascular outcomes.We have examined the cellular mechanisms involved in展开更多
文摘Aim Stable microtubules （MTs） is involved the mechanism of diabetic cardiomyopathy （DCM）, which is induced by acetylation of α-tubulin. The present study investigated whether SIRT2, a deacetylase, regulates MT stability through α-tubulin deacetylation in DCM and whether the receptor of advanced glycation end products （AGEs） signaling pathway is involved in this effect. Methods Type 1 diabetic mellitus （T1DM） rats model was established by a single intraperitoneal injection of streptozotocin （STZ, 65 mg · kg^-1） , and neonatal rat cardio- myocytes were also cultured. Heart function was detected by Doppler. MT stability was elevated by β-tubulin ex- pression density. The protein expression of SIRT2, acetylated α-tubulin and AGEs receptor were detected by immu- nohistochemistry or Western blots. The interaction of SIRT2 and acetylated α-tubulin was detected by Co-immuno- precipitation. Results In an animal model of T1DM, Western blot and immunohistochemistry revealed downregu- lation of SIRT2 but upregulation of the acetylated α-tubulin protein. These effects were reduced by treatment of aminoguanidine, an inhibitor of AGEs production. HDAC6 expression did not regulated in heart. In primary cul- tures of neonatal rat cardiomyocytes, the AGEs treatment impaired the SIRT2/acetylated α-tubulin signaling path- way, and SIRT2-overexpression reversed the function of AGEs on cardiomyocytes. In addition, gene silencing of AGEs receptor alleviated the impairment effect of AGEs on cardiomyocytes. Conclusion In conclusion, these data demonstrate that AGEs/AGEs receptor promote MT stabilization via the suppression of the SIRT2/acetylated α-tu- bulin signaling pathway in DCM development.
文摘越来越多的研究表明,晚期糖基化终产物（advanced glycation end products,AGEs）参与了神经系统退行性病变的过程,包括参与了阿尔茨海默病（Alzheimer disease,AD）的发病机制以及β-淀粉样蛋白（Aβ）的沉积,是AD的一个标志性特征。外源性AGEs形成于加热和辐照食品的过程中,
文摘Endothelial dysfunction,caused by declining impact of endothelium-derived relaxing factors and/or exaggerated production and activity of endothelium-derived contracting factors in the vascular wall,is the common consequence of diabetes and hypertension.The degree of endothelial dysfunction predicts future cardiovascular outcomes.We have examined the cellular mechanisms involved in
