Molecular mechanism of the regulating factors for sarcoplasmic reticulum Ca-ATPase

肌浆网Ca-ATP酶调节因子的分子机制

• 批准号: 17590249
• 负责人: ASAHI Michio
• 金额: $ 2.3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2006
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-17590249/
• 关键词: Proteins; Cardiovascular Medicine, hypertention; Stress

To examine the regulatory mechanism of cardiac type sarco(endo)plasmic reticulum Ca-ATPase(SERCA2a), which plays an important role in cardiac function, the primary cell culture of rat adult cardiomyocytes was espablished, and the physical profile and calcium transient of cardiomyocytes by electrical twitches were measured after various treatments. The research results are as follows. We investigated the effect of acrolein, an adduct of cigarette smoking, on cardiomyocytes. As a result, acrolein reduced the fuction of cardiomyocytes and eventually induced apoptosis. The apoptosis by acrolein was also induced in human umbilical vein endothelial cells (HUVEC), which might be involved in atherosclerosis related to cigarette smoking. The regulatory mechanism of cardiac ryanodine receptor, which is also the potent regulator of cardiac muscle, was examined. We found presenalin-2 as a regulator of cardiac ryanodine receptor. It was shown that presenalin-2 bound to cardiac ryanodine receptor in a calcium dependent manner and controlled the cardiac function. Furthermore, we revealed that phospholamban (PLN), an endogenous regulator of SERCA2a, was O-G1cNAcylated and the inhibitory function of PLN was regulated by the O-G1cNAcylation.

为探讨心肌型肌浆网钙ATP酶（SERCA 2a）的调节机制，建立了大鼠心肌细胞原代培养模型，并通过电刺激观察了心肌细胞的物理特性和钙瞬变。研究结果如下。我们研究了丙烯醛，吸烟的加合物，对心肌细胞的影响。结果表明，丙烯醛降低了心肌细胞的功能，并最终诱导了心肌细胞凋亡。丙烯醛还可诱导人脐静脉内皮细胞（HUVEC）凋亡，这可能与吸烟相关的动脉粥样硬化有关。研究了心肌兰尼碱受体的调节机制，该受体也是心肌的有效调节剂。我们发现早老素-2作为心脏ryanodine受体的调节剂。结果表明，早老素-2以钙依赖性方式与心肌ryanodine受体结合，控制心脏功能。此外，我们发现，受磷蛋白（PLN），SERCA 2a的内源性调节剂，是O-G1 cNAc酰化和PLN的抑制功能是由O-G1 cNAc酰化调节。

项目成果

The Asn418-linked N-glycan of ErbB3 plays a crucial role in preventing spontaneous heterodimerization and tumor promotion.

• DOI: 10.1158/0008-5472.can-06-3023
• 发表时间: 2007-03
• 期刊: Cancer research
• 影响因子: 11.2
• 作者: Shunichi Yokoe;Motoko Takahashi;M. Asahi;Seung Ho Lee;Wei Li;D. Osumi;E. Miyoshi;N. Taniguchi

活性酸素種のアポトーシスにおける役割

活性氧在细胞凋亡中的作用

• 发表时间: 2006
• 期刊: 酸化ストレス-フリーラジカル医学生物学の最前線 Ver.2
• 作者: 朝日通雄;朴用用軾;谷口直之
• 通讯作者: 谷口直之

Acrolein produces nitric oxide through the elevation of intracellular calcium levels to induce apoptosis in human umbilical vein endothelial cells: Implications for smoke angiopathy

• DOI: 10.1016/j.niox.2005.09.004
• 发表时间: 2006-03-01
• 期刊: NITRIC OXIDE-BIOLOGY AND CHEMISTRY
• 影响因子: 3.9
• 作者: Misonou, Y;Asahi, M;Taniguchi, N
• 通讯作者: Taniguchi, N

Progression of heart failure was suppressed by inhibition of apoptosis signal-regulating kinasel(ASK1) via transcoronary gene transfer.

通过跨冠状动脉基因转移抑制细胞凋亡信号调节激酶1（ASK1），从而抑制心力衰竭的进展。

• 发表时间: 2007
• 期刊: J Am Coll Cardiol. (In press)
• 作者: Sarama;R.H.M. ら;Shungo Hikoso et al.
• 通讯作者: Shungo Hikoso et al.

Acrolein induces Hsp72 via both PKCdelta/JNK and calcium signaling pathways in human umbilical vein endothelial cells.

丙烯醛通过人脐静脉内皮细胞中的 PKCdelta/JNK 和钙信号通路诱导 Hsp72。

• 发表时间: 2005
• 期刊: Free Radic Res. 39(5)
• 作者: Kimura;T.;Yoshiko Misonou
• 通讯作者: Yoshiko Misonou