Ataxia telangiectasia mutated kinase plays a protective role in β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling.
Ataxia telangiectasia mutated kinase plays a protective role in β-adrenergic receptor-stimulated cardiac myocyte apoptosis and myocardial remodeling.
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DOI：
10.1007/s11010-011-0769-6
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发表时间：
2011-07
影响因子：
4.3
通讯作者：
Singh, Krishna
中科院分区：
文献类型：
--
作者：
Foster, Cerrone R.;Singh, Mahipal;Subramanian, Venkateswaran;Singh, Krishna
β-Adrenergic receptor (β-AR) stimulation induces cardiac myocyte apoptosis and plays an important role in myocardial remodeling. Here we investigated expression of various apoptosis-related genes affected by β-AR stimulation, and examined first time the role of ataxia telangiectasia mutated kinase (ATM) in cardiac myocyte apoptosis and myocardial remodeling following β-AR stimulation. cDNA array analysis of 96 apoptosis-related genes indicated that β-AR stimulation increases expression of ATM in the heart. In vitro, RT-PCR confirmed increased ATM expression in adult cardiac myocytes in response to β-AR stimulation. Analysis of left ventricular structural and functional remodeling of the heart in wild-type (WT) and ATM heterozygous knockout mice (hKO) 28 days after ISO-infusion showed increased heart weight to body weight ratio in both groups. M-mode echocardiography showed increased percent fractional shortening (%FS) and ejection fraction (EF%) in both groups 28 days post ISO-infusion. Interestingly, the increase in %FS and EF% was significantly lower in the hKO-ISO group. Cardiac fibrosis and myocyte apoptosis were higher in hKO mice at baseline and ISO-infusion increased fibrosis and apoptosis to a greater extent in hKO-ISO hearts. ISO-infusion increased phosphorylation of p53 (Serine-15) and expression of p53 and Bax to a similar extent in both groups. hKO-Sham and hKO-ISO hearts exhibited reduced intact β1 integrin levels. MMP-2 protein levels were significantly higher, while TIMP-2 protein levels were lower in hKO-ISO hearts. MMP-9 protein levels were increased in WT-ISO, not in hKO hearts. In conclusion, ATM plays a protective role in cardiac remodeling in response to β-AR stimulation.
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影响因子：
3.3
作者：
Behonick, GS;Novak, MJ;Baskin, SI
通讯作者：
Baskin, SI
影响因子：
3
作者：
Bos, R;Mougenot, N;Lechat, P
通讯作者：
Lechat, P
影响因子：
64.5
作者：
Barlow, C;Hirotsune, S;WynshawBoris, A
通讯作者：
WynshawBoris, A
影响因子：
2
作者：
Hori, Yasutomo;Kunihiro, Shoh-ichi;Higuchi, Seiichi
通讯作者：
Higuchi, Seiichi
DOI：
10.1016/s0169-328x(97)00370-7
发表时间：
1998-03-30
期刊：
MOLECULAR BRAIN RESEARCH
影响因子：
--
作者：
Ghee, M;Baker, H;Ziff, EB
通讯作者：
Ziff, EB