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自发性高血压大鼠脑、心脏和肾脏中钙调蛋白相关蛋白的表达与定位

Expression and localization of calmodulin-related proteins in brain, heart and kidney from spontaneously hypertensive rats.

作者信息

Kameshima Satoshi, Okada Muneyoshi, Yamawaki Hideyuki

机构信息

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.

Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato University, Towada, Aomori 034-8628, Japan.

出版信息

Biochem Biophys Res Commun. 2016 Jan 15;469(3):654-8. doi: 10.1016/j.bbrc.2015.12.048. Epub 2015 Dec 15.

Abstract

Blood pressure is regulated not only by peripheral arterial resistance, but also by heart, kidney, and central nervous system. We have previously demonstrated that expression level of calmodulin-related proteins including eukaryotic elongation factor 2 kinase (eEF2K), death-associated protein kinase (DAPK)3, and histone deacetylase (HDAC)4 was specifically elevated in mesenteric artery from spontaneously hypertensive rats (SHR), which partly contributes to the development of hypertension via vascular inflammation and structural remodeling. We tested the hypothesis whether expression and localization of eEF2K, DAPK3, and HDAC4 are altered in brain, heart, and kidney from SHR. After brain, left ventricles (LV), and kidney were isolated from 12-week-old male Wistar Kyoto rats (WKY) and SHR, Western blotting and histological analysis were performed. In brain tissue, protein expression of eEF2K and HDAC4 was abundant, whereas DAPK3 protein was less. HDAC4 protein expression in SHR brain was significantly higher than that in WKY brain. In LV, protein expression of eEF2K was relatively higher than DAPK3 or HDAC4, and it was significantly higher in SHR than WKY. In kidney tissue, protein expression of DAPK3 was the highest and seemed to be localized specifically to renal tubule. The present results indicate that the increased HDAC4 in brain and increased eEF2K in LV might be at least in part related to the development of hypertension.

摘要

血压不仅受外周动脉阻力调节,还受心脏、肾脏和中枢神经系统调节。我们之前已经证明,包括真核生物延伸因子2激酶(eEF2K)、死亡相关蛋白激酶(DAPK)3和组蛋白去乙酰化酶(HDAC)4在内的钙调蛋白相关蛋白的表达水平在自发性高血压大鼠(SHR)的肠系膜动脉中特异性升高,这部分通过血管炎症和结构重塑导致高血压的发展。我们检验了以下假设:SHR的脑、心脏和肾脏中eEF2K、DAPK3和HDAC4的表达及定位是否发生改变。从12周龄雄性Wistar Kyoto大鼠(WKY)和SHR中分离出脑、左心室(LV)和肾脏后,进行了蛋白质印迹分析和组织学分析。在脑组织中,eEF2K和HDAC4的蛋白表达丰富,而DAPK3蛋白较少。SHR脑组织中HDAC4蛋白表达明显高于WKY脑组织。在LV中,eEF2K的蛋白表达相对高于DAPK3或HDAC4,且在SHR中明显高于WKY。在肾脏组织中,DAPK3的蛋白表达最高,似乎特异性定位于肾小管。目前的结果表明,脑中HDAC4增加和LV中eEF2K增加可能至少部分与高血压的发展有关。

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