INVOLVEMENT OF HUMAN PLASMA ANGIOTENSIN I-CONVERTING ENZYME IN THE DEGRADATION OF THE HAEMOREGULATORY PEPTIDE N-ACETYL-SERYL-ASPARTYL-LYSYL-PROLINE

被引:100
作者
RIEGER, KJ
SAEZSERVENT, N
PAPET, MP
WDZIECZAKBAKALA, J
MORGAT, JL
THIERRY, J
VOELTER, W
LENFANT, M
机构
[1] INST CHIM SUBST NAT,CNRS,F-91198 GIF SUR YVETTE,FRANCE
[2] UNIV TUBINGEN,INST PHYSIOL CHEM,PHYS BIOCHEM ABT,W-7400 TUBINGEN 1,GERMANY
[3] CENS,SERV BIOCHIM,INGN PROT LAB,F-91191 GIF SUR YVETTE,FRANCE
关键词
D O I
10.1042/bj2960373
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The degradation of N-Ac-Ser-Asp-Lys-Pro (AcSDKP), a negative regulator controlling the proliferation of the haematopoietic stem cell, by enzymes present in human plasma, has been investigated. Radiolabelled AcSD[4-H-3]KP ([H-3]AcSDKP, 1 mM) was completely metabolized in human plasma with a half-life of 80 min, leading exclusively to the formation of radiolabelled lysine. The cleavage of AcSDKP was insensitive to classical proteinase inhibitors including leupeptin, but sensitive to metalloprotease inhibitors. The degradation was completely blocked by specific inhibitors of angiotensin I-converting enzyme (ACE; kininase II; peptidyldipeptide hydrolase, EC 3.4.15.1), showing that the first step of the hydrolysis was indeed due to ACE. In dialysed plasma, the hydrolysis proceeded at only 17% of the maximal rate, whereas addition of 20 mM NaCl led to the recovery of the initial rate observed with normal plasma. Hydrolysis of AcSDKP by commercial rabbit lung ACE generated the C-terminal dipeptide Lys-Pro. Thus, ACE cleaves AcSDKP by a dipeptidyl carboxypeptidase activity. In fact the formation of Lys-Pro was observed when AcSDKP was incubated in human plasma in the presence of HgCl2. These results suggest that ACE is involved in the first limiting step of AcSDKP degradation in human plasma. The second step seems to be under the control of a leupeptin- and E-64-insensitive, HgCl2-sensitive plasmatic enzyme.
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页码:373 / 378
页数:6
相关论文
共 17 条
[1]   NEUTRAL ENDOPEPTIDASE 24.11 AND ANGIOTENSIN CONVERTING ENZYME LIKE ACTIVITY IN CALLA POSITIVE AND CALLA NEGATIVE LYMPHOID-CELLS [J].
BEAUMONT, A ;
BROUET, JC ;
ROQUES, BP .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1989, 160 (03) :1323-1329
[2]   AMELIORATION OF CHEMOTHERAPY-INDUCED TOXICITY BY COTREATMENT WITH ACSDKP, A TETRAPEPTIDE INHIBITOR OF HEMATOPOIETIC STEM-CELL PROLIFERATION [J].
BOGDEN, AE ;
CARDE, P ;
DEPAILLETTE, ED ;
MOREAU, JP ;
TUBIANA, M ;
FRINDEL, E .
ANNALS OF THE NEW YORK ACADEMY OF SCIENCES, 1991, 628 :126-139
[3]  
BUNNING P, 1983, BIOCHEMISTRY-US, V22, P103
[4]   NOVEL ACTIVITY OF ANGIOTENSIN-CONVERTING ENZYME - HYDROLYSIS OF CHOLECYSTOKININ AND GASTRIN ANALOGS WITH RELEASE OF THE AMIDATED C-TERMINAL DIPEPTIDE [J].
DUBREUIL, P ;
FULCRAND, P ;
RODRIGUEZ, M ;
FULCRAND, H ;
LAUR, J ;
MARTINEZ, J .
BIOCHEMICAL JOURNAL, 1989, 262 (01) :125-130
[5]  
Ehler MRW, 1990, HYPERTENSION PATHOPH, P1217
[6]  
FRINDEL E, 1977, EXP HEMATOL, V5, P74
[7]   INVOLVEMENT OF THYMOSIN-BETA-4 AND ENDOPROTEINASE ASP-N IN THE BIOSYNTHESIS OF THE TETRAPEPTIDE ACSERASPLYSPRO A REGULATOR OF THE HEMATOPOIETIC SYSTEM [J].
GRILLON, C ;
RIEGER, K ;
BAKALA, J ;
SCHOTT, D ;
MORGAT, JL ;
HANNAPPEL, E ;
VOELTER, W ;
LENFANT, M .
FEBS LETTERS, 1990, 274 (1-2) :30-34
[8]   ANGIOTENSIN CONVERTASE ACTIVITIES IN HUMAN ALVEOLAR MACROPHAGES - EFFECTS OF CIGARETTE-SMOKING AND SARCOIDOSIS [J].
HINMAN, LM ;
STEVENS, C ;
MATTHAY, RA ;
GEE, JBL .
SCIENCE, 1979, 205 (4402) :202-203
[9]   INHIBITOR OF HEMATOPOIETIC PLURIPOTENT STEM-CELL PROLIFERATION - PURIFICATION AND DETERMINATION OF ITS STRUCTURE [J].
LENFANT, M ;
WDZIECZAKBAKALA, J ;
GUITTET, E ;
PROME, JC ;
SOTTY, D ;
FRINDEL, E .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1989, 86 (03) :779-782
[10]   INHIBITOR OF STEM-CELL PROLIFERATION IN NORMAL BONE-MARROW [J].
LORD, BI ;
MORI, KJ ;
WRIGHT, EG ;
LAJTHA, LG .
BRITISH JOURNAL OF HAEMATOLOGY, 1976, 34 (03) :441-445