Platelet-activating factor acetylhydrolases in health and disease

被引:131
作者
Tjoelker, LW
Stafforini, DM
机构
[1] ICOS Corp, Bothell, WA 98021 USA
[2] Univ Utah, Huntsman Canc Inst, Salt Lake City, UT 84112 USA
来源
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS | 2000年 / 1488卷 / 1-2期
关键词
platelet-activating factor; acetylhydrolase; inflammation; animal model; clinic;
D O I
10.1016/S1388-1981(00)00114-1
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 platelet-activating factor (PAF) acetylhydrolases catalyze hydrolysis of the sn-2 ester bond of PAF and related proinflammatory phospholipids and thus attenuate their bioactivity. One secreted (plasma) and four intracellular isozymes have been described. The intracellular isozymes are distinguished by differences in primary sequence, tissue localization, subunit composition, and substrate preferences. The most thoroughly characterized intracellular isoform, Ib, is a G-protein-like complex with two catalytic subunits (alpha1 and alpha2) and a regulatory beta subunit. The beta subunit is a product of the LISI gene, mutations of which cause Miller-Dieker lissencephaly. Isoform II is a single polypeptide that is homologous to the plasma PAF acetylhydrolase and has antioxidant activity in several systems. Plasma PAF acetylhydrolase is also a single polypeptide with a catalytic triad of amino acids that is characteristic of the alpha/beta hydrolases. Deficiency of this enzyme has been associated with a number of pathologies. The most common inactivating mutation, V279F, is found ill > 30% of randomly surveyed Japanese subjects (4% homozygous, 27% heterozygous). The prevalence of the mutant allele is significantly greater in patients with asthma, stroke, myocardial infarction, brain hemorrhage, and nonfamilial cardiomyopathy, Preclinical studies have demonstrated that recombinant plasma PAF acetylhydrolase can prevent or attenuate pathologic inflammation in a number of animal models. In addition, preliminary clinical results suggest that the recombinant enzyme may have pharmacologic potential in human inflammatory disease as well. These observations underscore the physiological importance of the PAF acetylhydrolases and point toward new approaches for controlling pathologic inflammation. (C) 2000 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:102 / 123
页数:22
相关论文
共 194 条
[111]   Increased platelet-activating factor-acetylhydrolase activity in the umbilical venous plasma of growth-restricted fetuses [J].
Ohshige, A ;
Yoshimura, T ;
Maeda, T ;
Ito, M ;
Okamura, H .
OBSTETRICS AND GYNECOLOGY, 1999, 93 (02) :180-183
[112]   Cortisol and TGF-β inhibit secretion of platelet-activating factor-acetylhydrolase secretion in a monocyte-macrophage model system [J].
Okumura, KK ;
Sagawa, N ;
Ihara, Y ;
Kobayashi, F ;
Itoh, H ;
Mori, T .
MOLECULAR HUMAN REPRODUCTION, 1997, 3 (11) :927-932
[113]   THE ALPHA/BETA-HYDROLASE FOLD [J].
OLLIS, DL ;
CHEAH, E ;
CYGLER, M ;
DIJKSTRA, B ;
FROLOW, F ;
FRANKEN, SM ;
HAREL, M ;
REMINGTON, SJ ;
SILMAN, I ;
SCHRAG, J ;
SUSSMAN, JL ;
VERSCHUEREN, KHG ;
GOLDMAN, A .
PROTEIN ENGINEERING, 1992, 5 (03) :197-211
[114]  
ONeill C, 1996, ADV EXP MED BIOL, V416, P255
[115]   Reduced PAF-acetylhydrolase activity is associated with postinjury multiple organ failure [J].
Partrick, DA ;
Moore, EE ;
Moore, FA ;
Biffl, WL ;
Barnett, CC .
SHOCK, 1997, 7 (03) :170-174
[116]  
PATEL KD, 1992, J BIOL CHEM, V267, P15168
[117]   Regulation of platelet-activating factor (PAF) activity in human diseases by phospholipase A2 inhibitors, PAF acetylhydrolases, PAF receptor antagonists and free radical scavengers [J].
Peplow, PV .
PROSTAGLANDINS LEUKOTRIENES AND ESSENTIAL FATTY ACIDS, 1999, 61 (02) :65-82
[118]   Platelet-activating factor receptor activation - An initiator step in HIV-1 neuropathogenesis [J].
Perry, SW ;
Hamilton, JA ;
Tjoelker, LW ;
Dbaibo, G ;
Dzenko, KA ;
Epstein, LG ;
Hannun, Y ;
Whittaker, JS ;
Dewhurst, S ;
Gelbard, HA .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (28) :17660-17664
[119]  
*PHAS 2 PAF ARDS P, 2000, EUR SOC INT CAR MED
[120]   CORONARY VASOCONSTRICTION IN THE RAT, ISOLATED PERFUSED HEART INDUCED BY PLATELET-ACTIVATING-FACTOR IS MEDIATED BY LEUKOTRIENE-C4 [J].
PIPER, PJ ;
STEWART, AG .
BRITISH JOURNAL OF PHARMACOLOGY, 1986, 88 (03) :595-605