To examine the role of Epac, a new beta-adrenergic signaling molecule, for the development of heart failure

研究 Epac（一种新的 β-肾上腺素能信号分子）在心力衰竭发展中的作用

• 批准号: 20590871
• 负责人: OKUMURA Satoshi
• 金额: $ 3万
• 依托单位: Yokohama City University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2008
• 资助国家: 日本
• 起止时间: 2008 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-20590871/
• 关键词: サイクリックAMP; シグナル伝達; 循環器・高血圧; 心不全; 遺伝子改変マウス

It is well known that sympathetic and thus catecholamine signal is activated thereafter to compensate cardiac dysfunction. The mechanism of such compensation by catecholamine has been traditionally understood as PKA-mediated enforcement of cardiac contractility. We hypothesized that Epac, a new target of cAMP signal that functions independently from PKA, also plays a key role. Epac1 inhibited the Jak-STAT pathway and iNOS protein in the heart in response via IL-6. Activation of the cAMP/Epac pathway protected the heart against cytokine-induced cardiac dysfunction, suggesting a new role of catecholamine signal in compensating cardiac dysfunction in endotoxemia.

众所周知，交感神经信号和因此的儿茶酚胺信号随后被激活以补偿心脏功能障碍。传统上认为，这种由儿茶酚胺引起的代偿机制是PKA介导的心肌收缩力增强。我们假设Epac，一个独立于PKA发挥作用的cAMP信号的新靶点，也起着关键作用。Epac 1通过IL-6抑制心脏中的Jak-STAT通路和iNOS蛋白。cAMP/Epac通路的激活可保护心脏免受内毒素引起的心功能不全的影响，提示了儿茶酚胺信号在内毒素血症中补偿心功能不全的新作用。

项目成果

Activation of Epacl-specific Signaling Protects Heart from Cytokine-Mediated Cardiac Dysfunction through the inhibition of Proinflammatory Cytokine Signaling (Featured Research Scission)

Epacl 特异性信号传导的激活通过抑制促炎细胞因子信号传导来保护心脏免受细胞因子介导的心脏功能障碍（特色研究分会）

• 发表时间: 2009
• 作者: Okumura S;Suzuki S;Yunzhe B;Meihua J;Hidaka Y;Kurotani R;Ishikawa Y
• 通讯作者: Ishikawa Y

Identification of transcriptional factor E3 (TFE3) as a receptor-independent activator of Gα16 : Gene regulation by nuclear Gα subunit and its activator

鉴定转录因子 E3 (TFE3) 作为 Gα16 的受体非依赖性激活剂：核 Gα 亚基及其激活剂的基因调控

• 发表时间: 2011
• 期刊: J Biol Chem
• 影响因子: 4.8
• 作者: Sato M;Hiraoka M;Suzuki H;Bai Y;Kurotani R;Yokoyama U;Okumura S;Cismowski MJ;Lanier SM;Ishikawa Y
• 通讯作者: Ishikawa Y

Actibator of G protein signaling 8(AGS8)is required for hypoxia-induced apoptosis of cardiomyocytes : role of Gβγ and connexin 43(CX43)

缺氧诱导心肌细胞凋亡需要 G 蛋白信号传导 8 (AGS8) 激活剂：Gβγ 和连接蛋白 43 (CX43) 的作用

• 发表时间: 2009
• 期刊: J Biol Chem 284
• 作者: Sato M;Jiao Q;Honda T;Kurotani R;Toyota E;Okumura S;Takeya T;Minamisawa S;Lanier SM;Ishikawa Y
• 通讯作者: Ishikawa Y

The roles of cytochrome p450 in ischemic heart disease.

• DOI: 10.2174/138920011795713715
• 发表时间: 2011-06
• 期刊: Current drug metabolism
• 影响因子: 2.3
• 作者: Motohiko Sato;U. Yokoyama;T. Fujita;S. Okumura;Yoshihioro Ishikawa

Pharmacological activation of type 5 adenylyl cyclase stabilizes heart rate under microgravity induced by parabolic flight

5 型腺苷酸环化酶的药理激活可稳定抛物线飞行引起的微重力下的心率

• 发表时间: 2010
• 作者: Satoshi Okumura;Yunzhe Bai;Takashi Tsunematsu;Meihua Jin;Qibin Jiao;Sayaka Suzuki;Reiko Kurotani;Utako Yokoyama;Motohiko;Sato;Kousaku Iwatsubo;Yoshihiro Ishikawa
• 通讯作者: Yoshihiro Ishikawa