Epac activation inhibits IL-6-induced cardiac myocyte dysfunction.
Epac activation inhibits IL-6-induced cardiac myocyte dysfunction.
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DOI：
10.1007/s12576-016-0509-5
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发表时间：
2018-01
期刊：
影响因子：
--
通讯作者：
Ishikawa Y
中科院分区：
文献类型：
--
作者：
Jin H;Fujita T;Jin M;Kurotani R;Hidaka Y;Cai W;Suita K;Prajapati R;Liang C;Ohnuki Y;Mototani Y;Umemura M;Yokoyama U;Sato M;Okumura S;Ishikawa Y
促炎性细胞因子在感染性休克中释放并通过Jak-STAT途径损害心脏功能。众所周知，交感神经信号传导和因此的儿茶酚胺信号传导随后被激活以补偿心脏功能障碍。传统上认为，这种通过儿茶酚胺信号传导的补偿机制是环腺苷酸依赖性蛋白激酶（PKA）介导的心肌收缩力的增强。我们推测，由cAMP激活的交换蛋白（Epac），一个新发现的cAMP信号转导的靶点，其功能独立于PKA，也在这一机制中发挥关键作用。在培养的心肌细胞中，Epac的激活减弱了白细胞介素-6对异丙肾上腺素引起的细胞内Ca 2+浓度和收缩性增加的抑制作用，这很可能是通过SOCS 3抑制Jak-STAT通路，随后改变诱导型一氧化氮合酶表达。这些发现提示了儿茶酚胺信号在心力衰竭时补偿心功能障碍中的新作用。Epac及其下游通路可能成为治疗内毒素血症心功能不全的新靶点。
Pro-inflammatory cytokines are released in septic shock and impair cardiac function via the Jak-STAT pathway. It is well known that sympathetic and thus catecholamine signaling is activated thereafter to compensate for cardiac dysfunction. The mechanism of such compensation by catecholamine signaling has been traditionally understood to be cyclic AMP-dependent protein kinase (PKA)-mediated enforcement of cardiac contractility. We hypothesized that the exchange protein activated by cAMP (Epac), a newly identified target of cAMP signaling that functions independently of PKA, also plays a key role in this mechanism. In cultured cardiac myocytes, activation of Epac attenuated the inhibitory effect of interleukin-6 on the increase of intracellular Ca2+ concentration and contractility in response to isoproterenol, most likely through inhibition of the Jak-STAT pathway via SOCS3, with subsequent changes in inducible nitric oxide synthase expression. These findings suggest a new role of catecholamine signaling in compensating for cardiac dysfunction in heart failure. Epac and its downstream pathway may be a novel target for treating cardiac dysfunction in endotoxemia.
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影响因子：
56.9
作者：
Kawasaki, H;Springett, GM;Graybiel, AM
通讯作者：
Graybiel, AM
DOI：
10.1073/pnas.0812536106
发表时间：
2009-08-18
影响因子：
11.1
作者：
Cazorla, Olivier;Lucas, Alexandre;Lezoualc'h, Frank
通讯作者：
Lezoualc'h, Frank
影响因子：
64.8
作者：
Dodge-Kafka, KL;Soughayer, J;Scott, JD
通讯作者：
Scott, JD
影响因子：
20.1
作者：
Metrich, Melanie;Lucas, Alexandre;Lezoualc'h, Frank
通讯作者：
Lezoualc'h, Frank
影响因子：
5.5
作者：
Iwatsubo, Kousaku;Suzuki, Sayaka;Ishikawa, Yoshihiro
通讯作者：
Ishikawa, Yoshihiro