Neuroprotection factor of C-type natriuretic peptide (CNP)

C型利钠肽（CNP）神经保护因子

• 批准号: 18591596
• 负责人: NAGAYAMA Tetsuya
• 金额: $ 2.47万
• 依托单位: Kagoshima University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2006
• 资助国家: 日本
• 起止时间: 2006 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-18591596/
• 关键词: C-type natriuretic peptide; PACAP; ischemia; astrocytes; neuronal cell; endothelial cell; RIA; RT-PCR

C-type natriuretic peptide (CNP) belongs to the natriuretic peptide family and has a ring structure formed by an intramolecular disulfide bond, which is conserved among atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP),and CNP. ANP and BNP are mainly secreted from heart as cardiac hormones, whereas CNP is mainly localized in the central nervous system (CNS),but the function of CNP in the CNS has not been clarified so far. Receptors for natriuretic peptides are mainly guanylate cyclase-A (GC-A) and guanylate cyclase-B (GC-B). ANP and BNP show high affinity to GC-A, whereas, CNP preferentially binds to GC-B. Both GC-A and GC-B elicit an increase in intracellular cGMP that mediates most of the biological actions of natriuretic peptides. It has been reported that the neurotrophic peptide pituitary adenylate cyclase-activating polypeptide (PACAP)s timulates adenylate cyclase activity in cultured astrocytes. During the course of a study regarding the effect of PACAP on astrocytes with DNA microarray, we found that CNP gene expression was markedly increased in astrocytes stimulated by PACAP. Then, we tried to clarify how PACAP regulates the biosynthesis and secretion of CNP in the astrocytes. In rat-cultured astrocytes, pituitary PACAP activates gene expression and secretion of CNP in a dose- and time-dependent manner. These results suggest that PACAP might be involved in,the regulation of CNP biosynthesis in astrocytes.

C型利钠肽(CNP)属于利钠肽家族，具有由分子内二硫键形成的环状结构，在心房利钠肽(ANP)和脑利钠肽(BNP)中保守。 ANP和BNP主要作为心脏激素由心脏分泌,而CNP主要定位于中枢神经系统(CNS),但CNP在CNS中的功能迄今尚未阐明。利钠肽的受体主要是鸟苷酸环化酶-A (GC-A) 和鸟苷酸环化酶-B (GC-B)。 ANP和BNP对GC-A表现出高亲和力，而CNP优先与GC-B结合。 GC-A 和 GC-B 都会引起细胞内 cGMP 的增加，从而介导利尿钠肽的大部分生物作用。据报道，神经营养肽垂体腺苷酸环化酶激活多肽（PACAP）可刺激培养的星形胶质细胞中的腺苷酸环化酶活性。在利用 DNA 微阵列研究 PACAP 对星形胶质细胞的影响的过程中，我们发现 PACAP 刺激的星形胶质细胞中 CNP 基因表达显着增加。然后，我们试图阐明PACAP如何调节星形胶质细胞中CNP的生物合成和分泌。在大鼠培养的星形胶质细胞中，垂体 PACAP 以剂量和时间依赖性方式激活基因表达和 CNP 分泌。这些结果表明PACAP可能参与星形胶质细胞CNP生物合成的调节。

项目成果

The significance of multiple molecular forms of PACl as the basis for functional diversity of PACAP

PACl多种分子形式作为PACAP功能多样性基础的重要性

• 发表时间: 2008
• 作者: 上竹勇三郎;下澤達雄;Ushiyama M;Iwata S;宮田 篤郎;M. Ushiyama;S. Iwata;Ushiyama. Mina;Iwata Shinichi;Narimatsu S;Fujikawa K;Ushiyama M;Iwata S;Shimizu T;宮田 篤郎;S. Narimatsu;K. Fujikawa;M. Ushiyama;S. Iwata;T. Shimizu;Narimatsu S;Fujikawa K;Ushiyama M;Iwata S-I;Shimizu T;宮田 篤郎;Miyata A
• 通讯作者: Miyata A

多機能神経ペプチドPACAP受容体の構造と機能の多様性

多功能神经肽PACAP受体结构和功能的多样性

• 发表时间: 2006
• 期刊: 内分泌・糖尿病内科 22・4
• 作者: 上竹勇三郎;下澤達雄;Ushiyama M;Iwata S;宮田 篤郎;M. Ushiyama;S. Iwata;Ushiyama. Mina;Iwata Shinichi;Narimatsu S;Fujikawa K;Ushiyama M;Iwata S;Shimizu T;宮田 篤郎;S. Narimatsu;K. Fujikawa;M. Ushiyama;S. Iwata;T. Shimizu;Narimatsu S;Fujikawa K;Ushiyama M;Iwata S-I;Shimizu T;宮田 篤郎
• 通讯作者: 宮田 篤郎

C-type natriuretic peptide is specifically augmented by pituitary adenylate cyclase-activating polypeptide in rat astrocytes.

大鼠星形胶质细胞中的垂体腺苷酸环化酶激活多肽可特异性增强 C 型利钠肽。

• 发表时间: 2006
• 期刊: Ann. N. Y. Acad. Sci. 1070
• 作者: Fujikawa K;Minamino N;Miyata A;et. al.
• 通讯作者: et. al.

Changesintissuefactorandtheeffectsoftissuefactorpathway inhibitor on transient focal cerebral ischemia in rats

组织因子的变化及软组织因子通路抑制剂对大鼠短暂性局灶性脑缺血的影响

• 发表时间: 2008
• 期刊: Thromb Res. 112
• 作者: Gotoh;Tetsu;Shrestha Prabin;Niiro Masaki
• 通讯作者: Niiro Masaki

Changes in tissue factor and the effects of tissue factor pathway inhibitor on transient focal cerebral ischemia in rats

组织因子变化及组织因子途径抑制剂对大鼠短暂性局灶性脑缺血的影响

• 发表时间: 2008
• 期刊: Thromb Res. 112
• 作者: Masaki;Niiro;Tetsuya;Nagayama;Syunichi;Yunoue;Soichi;Obara;Hirofumi;Hirano
• 通讯作者: Hirano