Ushiro S, Mizoguchi K, Yoshida S, Jimi S, Fujiwara T, Yoshida M, Wei E T, Kitabgi P, Amagaya S, Ono M, Kuwano M
Department of Biochemistry, Kyushu University School of Medicine, Maidashi, Fukuoka, Japan.
FEBS Lett. 1997 Dec 1;418(3):341-5. doi: 10.1016/s0014-5793(97)01403-8.
To investigate if neurotensin (NT) could induce activation of urokinase-type plasminogen activator (uPA) in vascular endothelial cells, we utilized the acetyl-NT (8-13) analogue, TJN-950, in which the C-terminal leucine is reduced to leucinol. TJN-950 inhibited the binding of 125I-NT to membranes of newborn rat brains and of COS-7 cells transfected with rat NT receptor cDNA, but at 10(4) higher doses than NT (8-13). However, TJN-950 was as effective as NT in inducing the fibrinolytic activity in bovine vascular aortic and human umbilical vein endothelial cells, and enhanced the migration of vascular endothelial cells. Moreover, administration of TJN-950 induced neovascularization in the rat cornea in vivo. TJN-950 had no effect on expression of uPA, plasminogen activator inhibitor-1 or uPA receptor mRNA. The binding of 125I-TJN-950 to cell membranes was blocked by unlabeled uPA and TJN-950, but not the amino-terminal or 12-32 fragment of uPA. TJN-950 may enhance uPA activity in vascular endothelial cells by interacting with the uPA receptor, resulting in induction of angiogenesis.
为研究神经降压素（NT）是否能诱导血管内皮细胞中尿激酶型纤溶酶原激活剂（uPA）的激活，我们使用了乙酰化NT（8-13）类似物TJN-950，其中C末端的亮氨酸被还原为亮氨醇。TJN-950抑制125I-NT与新生大鼠脑细胞膜以及转染了大鼠NT受体cDNA的COS-7细胞膜的结合，但所需剂量比NT（8-13）高10^4倍。然而，TJN-950在诱导牛胸主动脉和人脐静脉内皮细胞的纤溶活性方面与NT一样有效，并增强了血管内皮细胞的迁移。此外，在体内给予TJN-950可诱导大鼠角膜新生血管形成。TJN-950对uPA、纤溶酶原激活剂抑制剂-1或uPA受体mRNA的表达没有影响。未标记的uPA和TJN-950可阻断125I-TJN-950与细胞膜的结合，但uPA的氨基末端或12-32片段则不能。TJN-950可能通过与uPA受体相互作用增强血管内皮细胞中的uPA活性，从而诱导血管生成。
