Research for the anti-thrombus and anti-inflammation of annexin-V

annexin-V抗血栓和抗炎作用的研究

• 批准号: 04671359
• 负责人: FUNAKOSHI Takayuki
• 金额: $ 1.34万
• 依托单位: Kumamoto University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04671359/
• 关键词: Annexin-V; Anticoagulant protein; Anticoagulant peptides; Antithrombus; Functional site; 抗炎症作用

Placental anticoagulant protein-I(PAP-I, T.Funakoshi et al., Biochemistry 26,5572(1987), purified from human placenta, is a member of annexin family of Ca^<2+>-dependent phospholipid binding proteins. Protein and cDNA sequence data show that PAP-I, II, III and IV correspond to annexin-V, IV, III and II, respectively (M.J.Crumpton and J.R.Dedman, Nature 345, 212(1990)). Annexin-V, the most abundant of these proteins, is composed of 319 amino acids containing four tandem repeats of 70-90 amino acid each (T.Funakoshi et al., Biochemistry 26,8087(1987)). Annexin-V inhibit the extrinsic and intrinsic pathways of blood coagulation and binds specifically to anionic phospholipid surfaces in the presence of Ca^<2+>. Annexin-V also inhibits the hydrolysis of phospholipid by phospholipase A2. This inhibition is thought to suppress prostaglandin synthesis leading to antiinflammatory action.The peptides, SHLRKV and DHTLIR, corresponding to annexin-V residues 204-209 and 266-271, respectively, are included in the functional site of annexin-V and exhibit a potent anticoagulant activity but the peptides in which alanine is substituted for histidine do not. At this time, we synthesized the both peptides and the other peptides, HDTLIR and HDTQPRVLD, to determine the relationship of the structures and function of these peptides. These peptides and annexin-V lowered the death rates of the pulmonary embolism in mice, respectively.

胎盘抗凝蛋白-I（PAP-1，T. Funakoshi等人，Biochemistry 26，5572（1987），从人胎盘中纯化，是Ca ^2+依赖性磷脂结合蛋白的膜联蛋白家族的成员。蛋白质和cDNA序列数据显示，PAP-1、II、III和IV分别对应于膜联蛋白-V、IV、III和II（M.J.Crumpton和J.R.Dedman，Nature 345，212（1990））。这些蛋白质中最丰富的膜联蛋白-V由319个氨基酸组成，含有四个串联重复序列，每个串联重复序列为70 - 90个氨基酸（T.Funakoshi et al.，Biochemistry 26，8087（1987））。膜联蛋白V抑制血液凝固的外在和内在途径，并在Ca ^2+存在下特异性结合阴离子磷脂表面。膜联蛋白-V还抑制磷脂酶A2对磷脂的水解。分别对应于膜联蛋白-V残基204 - 209和266 - 271的肽SHLRKV和DHTLIR被包括在膜联蛋白-V的功能位点中，并表现出有效的抗凝活性，但其中丙氨酸取代组氨酸的肽没有。在此基础上，我们合成了这两个肽以及另外两个肽HDTLIR和HDTQPRVLD，以确定这些肽的结构与功能的关系。这些肽和膜联蛋白-V分别降低了小鼠肺栓塞的死亡率。

项目成果

Takayuki Funakoshi, Hideaki Shimada, Shoji Kojima et al.: "Anticoagulant Action of Vanadate" Chem.Pharm.Bull.40. 174-176 (1992)

Takayuki Funakoshi、Hideaki Shimada、Shoji Kojima 等人：“钒酸盐的抗凝作用”Chem.Pharm.Bull.40。

古島浩二、船越崇行、島田秀昭、児島昭次: "ヒト胎盤由来抗凝固蛋白質(Annexin-V)に対する希土類金属の影響" 生化学. 64. 1003 (1992)

Koji Furushima、Takayuki Funakoshi、Hideaki Shimada、Shoji Kojima：“稀土金属对人胎盘来源的抗凝蛋白（Annexin-V）的影响”生物化学 64. 1003 (1992)。

船越崇行、島田秀昭、児島昭次他5名: "Anticoagulant Action of Vanadate" Chem.Pharm.Bull.40. 174-176 (1992)

Takayuki Funakoshi、Hideaki Shimada、Shoji Kojima 和其他 5 人：“钒酸盐的抗凝作用”Chem.Pharm.Bull.40 (1992)。

坂田光彦、真鍋史朗、折田正義、高宮修、船越崇行: "胎盤由来抗凝固蛋白質(PAP-I,Annexin-V)の疾患との関連" 臨床病理(Jpn.J.Clin.Pathol.). 41. 328 (1993)

Mitsuhiko Sakata、Shiro Manabe、Masayoshi Orita、Osamu Takamiya、Takayuki Funakoshi：“胎盘来源的抗凝蛋白（PAP-I、Annexin-V）与疾病的关系”临床病理学（Jpn. J. Clin. Pathol.）。 328 (1993)

船越崇行、島田秀昭、児島昭次 他5名: "Anticoagulant Action of Vanadate" Chem.Pharm.Bull.40. 174-176 (1992)

Takayuki Funakoshi、Hideaki Shimada、Shoji Kojima 和其他 5 人：“钒酸盐的抗凝作用”Chem.Pharm.Bull.40 (1992)。