Novel role of a Ca^<2+>-binding protein NCS-1 as a survival promoting factor

Ca^2结合蛋白NCS-1作为生存促进因子的新作用

• 批准号: 17590196
• 负责人: NISHITANI Tomoe
• 金额: $ 2.18万
• 依托单位: National Cardiovascular Center Research Institute
• 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-17590196/
• 关键词: Ca^<2+>-binding protein; Survival; Excitable cells

Molecular basis of survival from neuronal injury is essential for development of therapeutic strategy to remedy neurodegenerative disorders. Here, we demonstrate that neuronal Ca^<2+>-sensor 1 (NCS-1) ; one of key proteins for various neuronal functions also acts as an important neuronal survival factor. Overexpression of NCS-1 rendered cultured neurons more tolerant to cell death caused by several kinds of stressors ; while the dominant-negative mutant (E120Q) accelerated it. In addition, NCS-1 proteins increased upon treatment with glial cell line-derived neurotrophic factor (GDNF) and mediated GDNF-survival signal in a Akt-dependent but MAPK-independent manner. Furthermore, NCS-1 is significantly up-regulated in response to axotomy-induced injury in the DMV neurons of adult rats in vivo and adenoviral overexpression of E120Q resulted in a significant loss of surviving neurons, suggesting that NCS-1 is involved in anti-apoptotic mechanism in adult motor neurons. Taken together, we propose that NCS-1 is a novel survival-promoting factor up-regulated in injured neurons, mediating the GDNF-survival signal via Akt pathway.

神经元损伤后存活的分子基础对于开发治疗神经退行性疾病的治疗策略至关重要。在这里，我们证明了神经元Ca^2+传感器1（NCS-1），各种神经元功能的关键蛋白之一，也作为一个重要的神经元存活因子。NCS-1的过表达使培养的神经元对多种应激引起的细胞死亡具有更强的耐受性，而显性失活突变体（E120 Q）则加速了这种耐受性;此外，NCS-1蛋白在胶质细胞源性神经营养因子（GDNF）处理后表达增加，并以Akt依赖但MAPK不依赖的方式介导GDNF存活信号。此外，NCS-1在成年大鼠DMV神经元中响应于轴突切断诱导的损伤而显著上调，并且E120 Q的腺病毒过表达导致存活神经元的显著损失，表明NCS-1参与成年运动神经元中的抗凋亡机制。综上所述，我们认为NCS-1是一种新的在损伤神经元中上调的生存促进因子，通过Akt途径介导GDNF-生存信号。

项目成果

Selective induction of DeltaFosB in the brain after transient forebrain ischemia accompanied by an increased expression of galectin-1, and the implication of DeltaFosB and galectin-1 in neuroprotection and neurogenesis

短暂前脑缺血后大脑中选择性诱导 DeltaFosB 并伴有半乳糖凝集素 1 的表达增加，以及 DeltaFosB 和半乳糖凝集素 1 在神经保护和神经发生中的意义

• 发表时间: 2005
• 期刊: Cell Death Differ. 12
• 作者: Kurushima;H et al.
• 通讯作者: H et al.

Functional importance of charged residues within the putative intracellular loops in pH regulation by Na+/H+ exchanger NHE1

• DOI: 10.1111/j.1742-4658.2007.05962.x
• 发表时间: 2007-08-01
• 期刊: FEBS JOURNAL
• 影响因子: 5.4
• 作者: Hisamitsu, Takashi;N'amada, Keiji;Wakabayashi, Shigeo
• 通讯作者: Wakabayashi, Shigeo

Immunolocalization of KATP channel subunits in mouse and rat cardiac myocytes and the coronary vasculature.

• DOI: 10.1186/1472-6793-5-1
• 发表时间: 2005-01-12
• 期刊: BMC physiology
• 作者: Morrissey, Alison;Rosner, Erika;Coetzee, William A
• 通讯作者: Coetzee, William A

生化学 (動物細胞Na^+/H^+交換輸送体 : 分子から疾患まで)

生物化学（动物细胞Na^+/H^+交换转运蛋白：从分子到疾病）

• 发表时间: 2007
• 作者: Irie M;Terada T;Katsura T;Matsuoka S;Inui K;Shiozaki A;若林繁夫ら
• 通讯作者: 若林繁夫ら

(生物薬科学実験講座)細胞の増殖と成長因子 (III)培養細胞の利用

（生物制药科学实验课程）细胞增殖与生长因子（三）培养细胞的利用

• 发表时间: 2005
• 作者: Hasegawa I;Niisaro N;Iwasaki Y;Marunaka Y.;中村(西谷)友重ら
• 通讯作者: 中村(西谷)友重ら