我们的网站为什么显示成这样？

可能因为您的浏览器不支持样式，您可以更新您的浏览器到最新版本，以获取对此功能的支持，访问下面的网站，获取关于浏览器的信息：

|本期目录/Table of Contents|

MEK信号通路参与PTEN对心肌细胞肥大的负性调控(PDF)

《心脏杂志》[ISSN:1009-7236/CN:61-1268/R]

期数:
2008年第3期
页码:
264-267，272
栏目:
基础研究
出版日期:
2008-05-20

文章信息/Info

Title:
MEK1/ERK1/2 signal pathway involved in antimyocardial hypertrophyic effects of PTEN
作者:
速晓华; 李刚; 陈劲松; 杨永健
成都军区总医院心血管内科，四川 成都 610083
Author(s):
SU Xiaohua;  LI Gang;  CHEN Jinsong;  YANG Yongjian
Department of Cardiology, General Hospital, Chengdu Military Area Command, Chengdu 610083, Sichuan, China
关键词:
第10号染色体上同源丢失的磷酸酶张力蛋白基因; 细胞外信号调节激酶; 血管紧张素Ⅱ; 心肌肥大
Keywords:
phosphatase and tensin homology deleted on chromosome 10;  extracellular signalregulated kinase;  angiotension Ⅱ;  myocardial hypertrophy
分类号:
R322.11
DOI:
-
文献标识码:
A
摘要:
目的 探讨第10号染色体上同源丢失的磷酸酶张力蛋白（PTEN）基因的过度表达对血管紧张素Ⅱ（AngⅡ）诱导的心肌肥大的负性调控机制。方法 通过携带野生型PTEN基因的腺病毒(AdPTEN)感染，构建过度表达PTEN的原代培养的心肌细胞模型。以AngⅡ为促心肌肥大的刺激剂，采用RTPCR检测受感染细胞内心房钠尿肽（ANP）、β肌球蛋白重链（βMHC） mRNA的表达，用Western blot检测细胞外信号调节激酶1/2（ERK1/2）和磷酸化ERK1/2(pERK1/2)蛋白的表达。结果 AdPTEN感染后，心肌细胞内过度表达的PTEN mRNA和其蛋白，可明显抑制AngⅡ刺激所致心肌细胞肥大标志基因的表达。AngⅡ刺激可使ERK1/2与pERK1/2蛋白的表达明显增高；但PTEN的过度表达能明显抑制AngⅡ引起的ERK1/2与pERK1/2蛋白的表达。结论 PTEN能够负性调控AngⅡ刺激引起的心肌细胞肥大，MEK1/ERK1/2信号通路可能参与了PTEN的负性调控过程。
Abstract:
AIM To explore the mechanism by which PTEN acted as an endogenously negative regulator of myocardial hypertrophy induced by angiotension Ⅱ(Ang Ⅱ). METHODS Primarily cultured neonatal rat cardiomyocytes were infected with adenovirus containing PTEN gene, using empty adenovirus containing green fluorescent protein (GFP)(AdGFP) as control. AngⅡ served as a stimulus of accelerating myocardial hypertrophy, RTPCR was used to detect the level of atrial natriuretic protein (ANP), β myosin heavy chain (βMHC) mRNAs and Western blot was applied to detect the level of ERK1/2 and pERK1/2 proteins. RESULTS After AdPTEN infection, infection of AdPTEN resulted in PTEN overexpression in the cardiomyocytes. Overexpressed PTEN efficiently suppressed the expression of embryonic gene. AngⅡ stimulation was followed by the increase in expression of ERK1/2 and pERK1/2 proteins. Overexpressed PTEN significantly suppressed the expression of ERK1/2 and pERK1/2 proteins induced by AngⅡ. CONCLUSION Overexpression of PTEN in the cardiomyocytes can result in marked repression of myocardial hypertrophy induced by AngⅡ. MEK1/ERK1/2 signal pathway may be involved in this process.

参考文献/References

［1］ Li J, Yen C, Liaw D, et al. PTEN，a putative protein tyrosine phosphatase gene mutated in human brain, breast and prostate cancer[J]. Science, 1997, 275(5308):1943-1947.

[2] Schwartzbauer G, Robbins J. The tumor suppressor gene PTEN can regulate cardiac hypertrophy and survival [J]. J Biol Chem, 2001, 276(38):35786-35793.

[3] Crackower MA, Oudit GY, Kozieradzki I, et al. Regulation of myocardial contractility and cell size by distinct PI3KPTEN signaling pathways[J]. Cell, 2002, 110(6):737-749.

[4] 祝善俊,杨永健,于林君,等. 钙调神经磷酸酶信号通路与心肌细胞肥大[J]. 中华内科杂志, 2004, 43(1):19-21.

[5] 杨永健,祝善俊,祝之明,等. 细胞内钙调控剂对心肌细胞生长的作用[J]. 中华心血管病杂志, 2001, 29(1):45-47.

[6] Ravingerova T, Barancik M, Strniskova M. Mitogenactivated protein kinases: a new therapeutic target in cardiac pathology[J]. Mol Cell Biochem, 2003, 247(1-2):127-138.

[7] Bueno OF, Molkentin JD. Involvement of extracellular signalregulated kinases 1/2 in cardiac hypertrophy and cell death[J]. Circ Res, 2002, 91(9):776-781.

[8] Gu J, Tamura M, Yamada KM. Tumor suppressor PTEN inhibits integrin and growth factormediated mitogenactivated protein (MAP) kinase signaling pathways[J]. Cell Biol, 1998, 143(5):1375-1383.

[9] Yart A, Laffargue M, Mayeux P, et al. A critical role for phosphoinositide 3kinase upstream of Gab1 and SHP2 in the activation of ras and mitogenactivated protein kinases by epidermal growth factor[J]. Biol Chem, 2001, 276(12):8856-8864.

[10]Weng LP, Smith WM, Brown JL, et al. PTEN inhibits insulinstimulated MEK/MAPK activation and cell growth by blocking IRS1 phosphorylation and IRS1/Grb2/Sos complex formation in a breast cancer model[J]. Hum Mol Genet, 2001, 10(6):605-616.

[11]Weng LP, Brown JL, Baker KM, et al. PTEN blocks insulinmediated ETS2 phosphorylation through MAP kinase, independently of the phosphoinositide 3kinase pathway[J]. Hum Mol Genet, 2002, 11(15):1687-1696.

[12]Molkentin JD. CalcineurinNFAT signaling regulates the cardiac hypertrophic response in coordination with the MAPKs[J]. Cardiovasc Res, 2004, 63(3):467-475.

[13]Zou Y, Yao A, Zhu W, et al. Isoproterenol activates extracellular signalregulated protein kinases in cardiomyocytes through calcineurin[J]. Circulation, 2001, 104(1):102-108.

[14]Wang L, Proud CG. Ras/Erk signaling is essential for activation of protein synthesis by Gq proteincoupled receptor agonists in adult cardiomyocytes[J]. Circ Res, 2002, 91(9):821-829.

备注/Memo

备注/Memo:
收稿日期：2007-04-16.作者简介：速晓华，主治医师，硕士 Email:suxiaohua2005@sohu.com
更新日期/Last Update: