Caveolin and β1-integrin coordinate angiotensinogen expression in cardiac myocytes.
Caveolin and β1-integrin coordinate angiotensinogen expression in cardiac myocytes.
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DOI：
10.1016/j.ijcard.2012.09.131
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发表时间：
2013-09-20
影响因子：
3.5
通讯作者：
Dostal, David E.
中科院分区：
文献类型：
--
作者：
Lal, Hind;Verma, Suresh K.;Feng, Hao;Golden, Honey B.;Gerilechaogetu, Fnu;Nizamutdinov, Damir;Foster, Donald M.;Glaser, Shannon S.;Dostal, David E.
心脏的肾素-血管紧张素系统（RAS）已被牵连在介导的心肌细胞肥大和重塑，虽然负责调节局部RAS的生化机制知之甚少。Caveolin-1（Cav-1）/Cav-3双基因敲除小鼠表现出心肌肥大，而在体外使用甲基-β-环糊精（MβCD）破坏脂筏/Caveolae可消除心脏保护作用。在这项研究中，新生大鼠心室肌细胞（NRVM）被用来确定是否脂筏/小窝可能参与调节血管紧张素原（Ao）基因的表达，RAS系统的底物。MβCD处理引起Ao基因表达的时间依赖性上调，这与有丝分裂原活化蛋白激酶（MAP）ERK 1/2、p38和JNK磷酸化的差异调节有关。在MβCD处理后不久（2 ~ 30 min），JNK高度磷酸化，而ERK 1/2和p38的显著激活则发生在更晚的时间（2 ~ 4 h）。β 1D整合素是Mβ CD激活MAP激酶所必需的。药理学抑制ERK 1/2和JNK可增强Mβ CD诱导的Ao基因表达，而阻断p38可抑制这种反应。腺病毒介导的野生型p38α表达增强Mβ CD诱导的Ao基因表达，而显性负性p38α表达则阻断MβCD的刺激作用。Cav-3 siRNA的表达刺激Ao基因的表达，而Cav-3的过表达是抑制性的。Cav-1和Cav-3的表达水平受p38的正调控，但不受ERK 1/2和JNK的影响。总的来说，这些研究表明，脂筏/小窝耦合Ao基因表达的机制，涉及β1-整合素和MAP激酶家族成员的差异作用。
The cardiac renin-angiotensin system (RAS) has been implicated in mediating myocyte hypertrophy and remodeling, although the biochemical mechanisms responsible for regulating the local RAS are poorly understood. Caveolin-1 (Cav-1)/Cav-3 double-knockout mice display cardiac hypertrophy, and in vitro disruption of lipid rafts/caveolae using methyl-β-cyclodextrin (MβCD) abolishes cardiac protection. In this study, neonatal rat ventricular myocytes (NRVM) were used to determine whether lipid rafts/caveolae may be involved in the regulation of angiotensinogen (Ao) gene expression, a substrate of the RAS system. Treatment with MβCD caused a time-dependent upregulation of Ao gene expression, which was associated with differential regulation of mitogen-activated protein (MAP) kinases ERK1/2, p38 and JNK phosphorylation. JNK was highly phosphorylated shortly after MβCD treatment (2 – 30 min), whereas marked activation of ERK1/2 and p38 occurred much later (2 – 4 h). β1D-integrin was required for MβCD-induced activation of the MAP kinases. Pharmacologic inhibition of ERK1/2 and JNK enhanced MβCD-induced Ao gene expression, whereas p38 blockade inhibited this response. Adenovirus-mediated expression of wild-type p38α enhanced MβCD-induced Ao gene expression; conversely expression of dominant negative p38α blocked the stimulatory effects of MβCD. Expression of Cav-3 siRNA stimulated Ao gene expression, whereas overexpression of Cav-3 was inhibitory. Cav-1 and Cav-3 expression levels were found to be positively regulated by p38, but unaffected by ERK1/2 and JNK. Collectively, these studies indicate that lipid rafts/caveolae couple to Ao gene expression through a mechanism that involves β1-integrin and the differential actions of MAP kinase family members.
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影响因子：
8.3
作者：
Domenighetti, AA;Wang, Q;Delbridge, LMD
通讯作者：
Delbridge, LMD
影响因子：
2.1
作者：
Jorde, Ulrich P
通讯作者：
Jorde, Ulrich P
影响因子：
4.8
作者：
Kathuria, H;Cao, YX;Williams, MC
通讯作者：
Williams, MC
影响因子：
3
作者：
Bao, Weike;Behm, David J.;Yue, Tian-Li
通讯作者：
Yue, Tian-Li
DOI：
10.1073/pnas.0501345102
发表时间：
2005-08-09
影响因子：
11.1
作者：
Kim, HP;Wang, X;Choi, AMK
通讯作者：
Choi, AMK