Histamine deficiency suppresses murine haptoglobin production and modifies hepatic protein tyrosine phosphorylation

被引:14
作者
Hegyi, K
Fülöp, AK
Tóth, S
Buzás, E
Watanabe, T
Ohtsu, H
Ichikawa, A
Nagy, A
Falus, A
机构
[1] Semmelweis Univ, Dept Genet Cell & Immunobiol, H-1089 Budapest, Hungary
[2] Hungarian Acad Sci, Mol Immunol Res Grp, Budapest, Hungary
[3] Mt Sinai Hosp, Samuel Lunenfeld Res Inst, Toronto, ON M5G 1X5, Canada
[4] Kyoto Univ, Grad Sch Pharmaceut Sci, Dept Physiol Chem, Kyoto, Japan
[5] Tohoku Univ, Sch Med, Dept Cellular Pharmacol 1, Sendai, Miyagi 980, Japan
关键词
histamine; knockout; acute phase protein; haptoglobin; tyrosine phosphorylation;
D O I
10.1007/PL00000906
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
Histidine decarboxylase (HDC) synthesizes endogenous histamine from histidine in mammals. HDC-deficient mice (HDC-/-), if kept on a histamine-free diet, have no histamine in their tissues. HDC-/- mice show multiple phenotypes. In this study we show that both the constitutively expressed and turpentine-induced level of an acute-phase protein, haptoglobin, is significantly lower in the serum of HDC-/- mice compared to that of wildtype animals. This effect was abolished if HDC gene-targeted mice received histamine-rich food. No differences were found when lipopolysaccharide (LPS) was used to induce the acute-phase reaction. Using specific antibodies to phosphorylated tyrosine, we showed that protein tyrosine phosphorylation (Y-P) of similar to 50- and 26- to 27-kDa liver proteins is significantly decreased in HDC-/- mice, but that the difference was largely diminished if the animals were kept on a histamine-rich diet, suggesting that the phenotype with lower haptoglobin production is diet inducible. Upon in vivo treatment with LPS, Y-P band intensity decreased, regardless of the presence or absence of histamine. Identification of elements of the signalling pathway with decreased phosphorylation may elucidate the molecular background of the effect of endogenous histamine in the hepatic acute-phase reaction.
引用
收藏
页码:850 / 854
页数:5
相关论文
共 34 条
[1]   THE ACUTE-PHASE RESPONSE [J].
BAUMANN, H ;
GAULDIE, J .
IMMUNOLOGY TODAY, 1994, 15 (02) :74-80
[2]   HISTAMINE AS AN AUTOCRINE GROWTH-FACTOR IN EXPERIMENTAL MAMMARY CARCINOMAS [J].
CRICCO, GP ;
DAVIO, CA ;
MARTIN, G ;
ENGEL, N ;
FITZSIMONS, CP ;
BERGOC, RM ;
RIVERA, ES .
AGENTS AND ACTIONS, 1994, 43 (1-2) :17-20
[3]   INTERLEUKIN-3 PROMOTES HISTAMINE SYNTHESIS IN HEMATOPOIETIC PROGENITORS BY INCREASING HISTIDINE-DECARBOXYLASE MESSENGER-RNA EXPRESSION [J].
DY, M ;
MACHAVOINE, F ;
LEBEL, B ;
ICHIKAWA, A ;
GASTINEL, LN ;
SCHNEIDER, E .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 1993, 192 (01) :167-173
[4]  
FALUS A, 1993, IMMUNOLOGY, V78, P193
[5]   STIMULATION OF HISTAMINE-RECEPTORS OF HUMAN MONOCYTOID AND HEPATOMA-DERIVED CELL-LINES AND MOUSE HEPATOCYTES MODULATES THE PRODUCTION OF THE COMPLEMENT COMPONENT-C3, COMPONENT-C4, FACTOR-B, AND COMPONENT-C2 [J].
FALUS, A ;
WALCZ, E ;
BROZIK, M ;
ROKITA, H ;
FUST, G ;
HAJNAL, A ;
MERETEY, K .
SCANDINAVIAN JOURNAL OF IMMUNOLOGY, 1989, 30 (02) :241-248
[6]   HISTAMINE MODULATES THE ACUTE-PHASE RESPONSE AT MULTIPLE POINTS [J].
FALUS, A .
IMMUNOLOGY TODAY, 1994, 15 (12) :596-596
[7]  
FALUS A, 1987, IMMUNOLOGY, V60, P547
[8]  
HILL SJ, 1990, PHARMACOL REV, V42, P45
[9]   The Croonian Lecture 1997. The phosphorylation of proteins on tyrosine: Its role in cell growth and disease [J].
Hunter, T .
PHILOSOPHICAL TRANSACTIONS OF THE ROYAL SOCIETY B-BIOLOGICAL SCIENCES, 1998, 353 (1368) :583-605
[10]   Gastrin-producing endocrine cells:: A novel source of histamine in the rat stomach [J].
Hunyady, B ;
Zólyomi, A ;
Hoffman, BJ ;
Mezey, É .
ENDOCRINOLOGY, 1998, 139 (10) :4404-4415