Proneurotensin 1-117, a stable neurotensin precursor fragment identified in human circulation

被引:43
作者
Ernst, A.
Hellmich, S.
Bergmann, A.
机构
[1] SphingTec GmbH, D-16556 Borgsdorf, Germany
[2] BRAHMS AG, Hennigsdorf, Germany
关键词
prohormone; neurotensin; neuromedin N; pro NT/NMN 1-117; mass spectrometry; sandwich immunoassay; half-life;
D O I
10.1016/j.peptides.2006.01.021
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
Proneurotensin/neuromedin N (pro NT/NMN) is the common precursor of two biologically active peptides, neurotensin (NT) and neuromedin N (NMN). We have established antibodies against peptide sequences of the NT/NMN precursor and developed a sandwich immunoassay for the detection of pro NT/NMN immunoreactivity in human circulation. Endogenous pro NT/NMN immunoreactivity was enriched by affinity chromatography using antibodies against two different pro NT/NMN epitopes, and further purified by reversed phase HPLC. Mass spectrometry analysis revealed pro NT/NMN 1-117 as major pro NT/NMN immunoreactivity in human circulation. Pro NT/NMN 1-117 is detectable in serum from healthy individuals (n = 124; median 338.9 pmol/L). As known for NT, the release of pro NT/NMN 1-117 from the intestine into the circulation is stimulated by ingestion of an ordinary meal. Investigation of the pro NT/NMN 1-117 in vitro stability in human serum and plasma revealed that this molecule is stable for at least 48 h at room temperature. Since pro NT/ NMN 1-117 is theoretically produced during precursor processing in stoichiometric amounts relative to NT and NMN, it could be a surrogate marker for the release of these bioactive peptides. (c) 2006 Elsevier Inc. All rights reserved.
引用
收藏
页码:1787 / 1793
页数:7
相关论文
共 42 条
[1]   ROLE OF ENDOPEPTIDASE-3.4.24.16 IN THE CATABOLISM OF NEUROTENSIN, IN-VIVO, IN THE VASCULARLY PERFUSED DOG ILEUM [J].
BARELLI, H ;
FOXTHRELKELD, JET ;
DIVE, V ;
DANIEL, EE ;
VINCENT, JP ;
CHECLER, F .
BRITISH JOURNAL OF PHARMACOLOGY, 1994, 112 (01) :127-132
[2]   CLONING OF HUMAN NEUROTENSIN NEUROMEDIN-N GENOMIC SEQUENCES AND EXPRESSION IN THE VENTRAL MESENCEPHALON OF SCHIZOPHRENICS AND AGE SEX MATCHED CONTROLS [J].
BEAN, AJ ;
DAGERLIND, A ;
HOKFELT, T ;
DOBNER, PR .
NEUROSCIENCE, 1992, 50 (02) :259-268
[3]   Prohormone and proneuropeptide processing - Recent progress and future challenges [J].
Beinfeld, MC .
ENDOCRINE, 1998, 8 (01) :1-5
[4]   IMMUNOLOGICAL AND BIOCHEMICAL-CHARACTERIZATION OF PROCESSING PRODUCTS FROM THE NEUROTENSIN NEUROMEDIN-N PRECURSOR IN THE RAT MEDULLARY-THYROID CARCINOMA-6-23 CELL-LINE [J].
BIDARD, JN ;
DENADAI, F ;
ROVERE, C ;
MOINIER, D ;
LAUR, J ;
MARTINEZ, J ;
CUBER, JC ;
KITABGI, P .
BIOCHEMICAL JOURNAL, 1993, 291 :225-233
[5]   HYPOTHERMIA AND INTOLERANCE TO COLD INDUCED BY INTRACISTERNAL ADMINISTRATION OF HYPOTHALAMIC PEPTIDE NEUROTENSIN [J].
BISSETTE, G ;
NEMEROFF, CB ;
LOOSEN, PT ;
PRANGE, AJ ;
LIPTON, MA .
NATURE, 1976, 262 (5569) :607-609
[6]   Cardiac peptide stability, aprotinin and room temperature: importance for assessing cardiac function in clinical practice [J].
Buckley, MG ;
Marcus, NJ ;
Yacoub, MH .
CLINICAL SCIENCE, 1999, 97 (06) :689-695
[7]  
CARRAWAY R, 1973, J BIOL CHEM, V248, P6854
[8]  
CARRAWAY RE, 1990, J BIOL CHEM, V265, P8627
[9]   TISSUE-SPECIFIC PROCESSING OF NEUROTENSIN NEUROMEDIN-N PRECURSOR IN CAT [J].
CARRAWAY, RE ;
MITRA, SP ;
JOYCE, TJ .
REGULATORY PEPTIDES, 1993, 43 (1-2) :97-106
[10]   CHARACTERIZATION OF LARGE NEUROMEDIN-N USING ANTISERA TOWARDS REGIONS OF THE NEUROTENSIN NEUROMEDIN-N PRECURSOR [J].
CARRAWAY, RE ;
MITRA, SP ;
PARADISE, C .
PEPTIDES, 1991, 12 (03) :601-607