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Dyrk1A经ASF调控CaMKⅡδ可变剪接在肾血管性高血压大鼠心肌肥厚中的作用 被引量：1

Effects of Dryk1A,ASF and alternative splicing of CaMKⅡδ on myocardial hypertrophy in renovascular hypertensive rats
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摘要 目的:探讨双特异性酪氨酸磷酸化调节激酶1A(Dyrk1A)经可变剪接因子(ASF)对钙/钙调素依赖蛋白激酶Ⅱδ(CaMKⅡδ)可变剪接的调控在肾血管性高血压大鼠心肌肥厚中的作用。方法:制备两肾一夹肾血管性高血压大鼠模型,给予Dyrk1A抑制剂表没食子儿茶素没食子酸酯(EGCG)和哈尔碱(harmine)干预,观察大鼠血压及心肌肥厚程度变化,逆转录-多聚酶链反应法检测CaMKⅡδ可变剪接的改变,免疫印迹法检测大鼠心肌Dyrk1A和ASF蛋白质表达的变化。结果:两肾一夹术后8周,与假手术组相比,手术组大鼠血压显著升高(P<0.05),大鼠左室重、左室重/体重比值及心肌细胞面积均增高(P<0.05),同时该组大鼠心肌中Dyrk1A蛋白表达增加,ASF蛋白表达下降(P<0.05),CaMKⅡδ亚型可变剪接表现为CaMKⅡδA、δB mRNA表达升高,δC mRNA表达降低(P<0.05);与手术组相比,EGCG和哈尔碱组大鼠左室重、左室重/体重比值和心肌细胞面积下降,同时大鼠心肌中Dyrk1A蛋白表达降低,ASF蛋白表达上调,CaMKⅡδ亚型可变剪接逆转(均P<0.05)。结论:Dyrk1A可通过ASF调控CaMKⅡδ的可变剪接,从而参与肾血管性高血压大鼠心肌肥厚的发生。 AIM： To investigate the role of dual -specificity tyrosine phosporylation- regulated kinase 1A （Dyrk1A） - alternative splicing factor （ASF） - calcium/calmodulin - dependent protein kinase Ⅱ δ（ CaMK Ⅱ δ） pathway in the progression of myocardial hypertrophy in renovascular hypertensive rats. METHODS ： The renovascular hypertension was induced by two- kidney one- clip （2K1C） method. The changes of blood pressure and myocardial hypertrophy were measured. The techniques of RT - PCR and Western blotting were used to detect CaMK Ⅱ δ alternative splicing and the pro- tein expression of Dyrk1 A and ASF, respectively. RESULTS： Eight weeks after operation, systolic blood pressure （SBP） and diastolic blood pressure （DBP） in 2K1C rats increased （P 〈 0. 05 ）. The increases in left ventricular weight （ LVW）, the ratio of LVW to body weight （BW） and the area of myocardial cells indicated that the hypertensive rats developed sig- nificant cardiac hypertrophy. The protein expression of Dyrk1A and mRNA expression of CaMK Ⅱ δA and δB were signifi- cantly increased, while the protein expression of ASF and mRNA expression of CaMK Ⅱ δC were decreased compared with sham - operated control rats （ P 〈 0. 05）. Treatment with Drykl A inhibitor epigallocatechin gallate （EGCG） or harmine ef- fectively attenuated cardiac hypertrophy and reversed the changes in the protein expression of Dyrk1 A, ASF and alternative splicing of CaMK Ⅱδ （ all P 〈 0. 05 ）. CONCLUSION ： Dyrk1A - ASF - CaMK Ⅱ δ pathway plays a role in the develop- ment of myocardial hypertrophy in renovascular hypertensive rats.
作者 姚健 朱健华 陆尽亚 秦晓同 于小红 盛红专
机构地区 南通大学附属医院心内科 南通大学医学院组胚教研室 南通大学南通市第一人民医院老年医学科
出处 《中国病理生理杂志》 CAS CSCD 北大核心 2012年第12期2125-2129,共5页 Chinese Journal of Pathophysiology
基金 国家自然科学基金资助项目(No.30971224 No.30971223) 江苏省教育厅课题资助项目(No.07KJD310170)
关键词 钙 钙调素依赖蛋白激酶Ⅱ 双特异性酪氨酸磷酸化调节激酶1A 可变剪接因子 大鼠 心肌肥厚 Calcium/calmodulin - dependent protein kinase Ⅱ Dual - specificity tyrosine phosphorylation - regulated kinase 1 A Alternative splicing factor Rats Myocardial hypertrophy
分类号 R542 [医药卫生—心血管疾病]
  • 相关文献

参考文献15

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共引文献4

同被引文献18

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  • 5Mishra S,Ling H,Grimm M. Cardiac hypertrophy and heart failure development through Gq and CaM kinase Ⅱ signaling[J].{H}Journal of Cardiovascular Pharmacology,2010.598-603.
  • 6Shi J,Zhang T,Zhou C. Increased dosage of Dyrk1A alters alternative splicing factor (ASF)-regulated alternative splicing of tau in Down syndrome[J].{H}Journal of Biological Chemistry,2008.28660-28669.
  • 7Gu Q,Jin N,Sheng H. Cyclic AMP-dependent protein kinase A regulates the alternative splicing of CaMK Ⅱ δ[J].PLoS One,2011.e25745.
  • 8Xu X,Yang D,Ding JH. ASF/SF2-regulated CaMK Ⅱ delta alternative splicing temporally reprograms excitation-contraction coupling in cardiac muscle[J].{H}CELL,2005.59-72.
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  • 10Mishra S,Ling H,Grimm M. Cardiac hypertrophy and heart failure development through Gq and CaM kinase Ⅱ signaling[J].{H}Journal of Cardiovascular Pharmacology,2010.598-603.

二级引证文献3

中国病理生理杂志
2012年 第12期

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