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Physiological significance of human placental aminopeptidases

人胎盘氨肽酶的生理意义

基本信息

批准号：
05454444
负责人：
MIZUTANI Shigehiko
金额：
$ 3.97万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1993
资助国家：
日本
起止时间：
1993 至 1995
项目状态：
已结题

项目摘要

We tried to understand pathophysiology in pregnancy via interrelationship between bioactive peptide hormones and their degradation proteases in placenta.1. Basic Research We showed the following evidences :(1) We isolated a cDNA clone with 4084 base pairs encoding P-LAP from a human placental cDNA library. The deduced suquence contains a hydrophobic region near the N terminus, suggesting that the enzyme is a type II intergral membrane protein.(2) The oxytocin and vasopressin degradation protease in human placenta is P-LAP.(3) The somatostatin degradation protease in human placenta is P-LAP.P-LAP might be involved in the development of the fetus via regulation not only the concentration of somatostatin but also vasoactive peptides such as vasopressin in the feto-placental circulation.(4) The initiating protease of angiotensin II degradation in human placental in aminopeptidase A and aminopeptidase N (AP-N).(5) Placental AP-N (CD13) degrades immunomodulating peptides such as tuftsin, thymopentin and splenopentin. AP-N might be involved in the immunology of pregnancy via regulating the concentration of immunomodulating peptides.2. Clinical Research We showed the following evidences :(1) Aminopepidase P,which might degrade bradykinin, increases in pregnancy sera with advancing gestation.(2) P-LAP in useful for monitoring post date pregnancy and premature delivery.(3) We found the significant correlation between pulsed Doppler S/D ratio and P-LAP activity in normal pregnancy. The P-LAP activity in pregnancy sera might reflect the vascular resistance in umbilical artery via regulation the concentration of fetal vasopression.

我们试图通过胎盘中生物活性肽激素与其降解蛋白酶之间的相互关系来了解妊娠的病理生理学。1。基础研究我们得到了以下证据：(1)从人胎盘cDNA文库中分离得到编码P-LAP的4084个碱基对的cDNA克隆。推导的序列在N末端附近含有一个疏水区，表明该酶是II型整合膜蛋白。(2)人胎盘中的催产素和加压素降解蛋白酶是P-LAP。(3)人胎盘中的生长抑素降解蛋白酶是P-LAP。P-LAP可能不仅通过调节胎儿的生长发育，还通过调节胎儿的发育。 (4) 人胎盘中氨肽酶 A 和氨肽酶 N (AP-N) 中血管紧张素 II 降解的起始蛋白酶。(5) 胎盘 AP-N (CD13) 降解免疫调节肽，如促生长素、胸腺五肽和脾喷丁。 AP-N可能通过调节免疫调节肽的浓度参与妊娠免疫。 2．临床研究我们显示了以下证据：(1) 氨基肽酶 P 可能会降解缓激肽，随着妊娠的进展，妊娠血清中的氨基肽酶 P 会增加。(2) P-LAP 可用于监测过期妊娠和早产。(3) 我们发现正常妊娠中脉冲多普勒 S/D 比值与 P-LAP 活性之间存在显着相关性。妊娠血清中P-LAP活性可能通过调节胎儿血管加压浓度来反映脐动脉血管阻力。