PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility.
PICOT is a critical regulator of cardiac hypertrophy and cardiomyocyte contractility.
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DOI：
10.1016/j.yjmcc.2008.09.124
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发表时间：
2008-12
影响因子：
5
通讯作者：
Park, Woo Jin
中科院分区：
文献类型：
--
作者：
Cha, Hyeseon;Kim, Ji Myoung;Oh, Jae Gyun;Jeong, Moon Hee;Park, Chang Sik;Park, Jaeho;Jeong, Hyeon Joo;Park, Byung Keon;Lee, Young-Hoon;Jeong, Dongtak;Yang, Dong Kwon;Bernecker, Oliver Y.;Kim, Do Han;Hajjar, Roger J.;Park, Woo Jin
PICOT（硫氧还蛋白的PKC相互作用表兄弟）先前显示可抑制心肌肥大的发展，同时增加心肌细胞收缩力。为了探索PICOT在心脏中的生理功能，我们通过使用基因捕获方法产生PICOT缺陷小鼠系。PICOT−/−小鼠是胚胎致死的，表明PICOT在胚胎发生过程中起着重要作用，而PICOT+/−小鼠是可行的，没有明显的形态缺陷。PICOT+/−小鼠心脏中的PICOT蛋白水平降低了约50%。相对于野生型同窝出生小鼠，PICOT+/−小鼠的压力超负荷诱导了显著加重的心脏肥大。与这一观察结果一致，PICOT+/−小鼠心脏中的压力超负荷极大地增强了钙调神经磷酸酶-NFAT信号传导。PICOT+/−小鼠的心肌细胞表现出显著降低的收缩力，这可能部分归因于受磷蛋白的低磷酸化和SERCA活性降低。这些数据表明精确的PICOT蛋白水平显著影响心脏肥大和心肌细胞收缩性的过程。我们认为PICOT在心肌肥厚中起着重要的负性调节和正性肌力调节作用。
PICOT (PKC-interacting cousin of thioredoxin) was previously shown to inhibit the development of cardiac hypertrophy, concomitant with an increase in cardiomyocyte contractility. To explore the physiological function of PICOT in the hearts, we generated a PICOT-deficient mouse line by using a gene trap approach. PICOT−/− mice were embryonic lethal indicating that PICOT plays an essential role during embryogenesis, whereas PICOT+/− mice were viable with no apparent morphological defects. The PICOT protein levels were reduced by about 50% in the hearts of PICOT+/− mice. Significantly exacerbated cardiac hypertrophy was induced by pressure overload in PICOT+/− mice relative to that seen in wild type littermates. In line with this observation, calcineurin-NFAT signaling was greatly enhanced by pressure overload in the hearts of PICOT+/− mice. Cardiomyocytes from PICOT+/− mice exhibited significantly reduced contractility, which may be due in part to hypophosphorylation of phospholamban and reduced SERCA activity. These data indicate that the precise PICOT protein level significantly affects the process of cardiac hypertrophy and cardiomyocyte contractility. We suggest that PICOT plays as a critical negative regulator of cardiac hypertrophy and a positive inotropic regulator.
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影响因子：
20.1
作者：
Jeong, Dongtak;Kim, Ji Myoung;Park, Woo Jin
通讯作者：
Park, Woo Jin
DOI：
10.1016/s0735-1097(98)00407-0
发表时间：
1998-11-01
影响因子：
24
作者：
Haider, AW;Larson, MG;Levy, D
通讯作者：
Levy, D
影响因子：
6.4
作者：
Ren J;Wold LE
通讯作者：
Wold LE
DOI：
10.1152/ajpheart.00214.2005
发表时间：
2006-02-01
影响因子：
4.8
作者：
Ji, Y;Zhao, W;Dedman, JR
通讯作者：
Dedman, JR
影响因子：
4.8
作者：
Chu, GX;Lester, JW;Kranias, EG
通讯作者：
Kranias, EG