SIRT2 regulates microtubule stabalization in diabetic cardiomyopath＇.  

出　　处：《中国药理学通报》2015年第B11期189-190,共2页Chinese Pharmacological Bulletin

摘　　要：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.

关 键 词：SIRT2 acetylated Α-TUBULIN diabetic CARDIOMYOPATHY MICROTUBULE stabilization ADVANCED glycationend PRODUCTS receptor for ADVANCED glycation end PRODUCTS AMINOGUANIDINE 

分 类 号：R[医药卫生]