Plasma platelet activating factor-acetylhydrolase (PAF-AH).
The platelet-activating factor-acetylhydrolase (PAF-AH) is an enzyme which catalyzes the hydrolysis of acetyl ester at the sn-2 position of PAF. The family of PAF-AHs consists of two intracellular isoforms (Ib and II), and one secreted isoform (plasma). These PAF-AHs show different biochemical characteristics and molecular structures. Plasma PAF-AH and intracellular isoform, II degrade not only PAF but also oxidatively fragmented phospholipids with potent biological activities. Among these PAF-AHs, plasma PAF-AH has been the target of many clinical studies in inflammatory diseases, such as asthma, sepsis, and vascular diseases, because the plasma PAF-AH activity in the patients with these diseases is altered when compared with normal individuals. Finding a genetic deficiency in the plasma PAF-AH opened the gate in elucidating the protecting role of this enzyme in inflammatory diseases. The most common loss-of-function mutation, V279F, is found in more than 30% of Japanese subjects (4% homozygous, 27% heterozygous). This single nucleotide polymorphism in plasma PAF-AH and the resulting enzymatic deficiency is thought to be a genetic risk factor in various inflammatory diseases in Japanese subjects. Administration of recombinant plasma PAF-AH or transfer of the plasma PAF-AH gene improves pathology in animal models. Therefore, substitution of plasma PAF-AH would be an effective in the treatment of the patients with the inflammatory diseases and a novel clinical approach. In addition, the detection of polymorphisms in the plasma PAF-AH gene and abnormalities in enzyme activity would be beneficial in the diagnosis of the inflammatory diseases.
Karasawa
Ken
K
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, Kanagawa, Japan. karasawa@pharm.teikyo-u.ac.jp
Harada
Ayako
A
Satoh
Noriko
N
Inoue
Keizo
K
Setaka
Morio
M
D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase; D000707:Anaphylaxis / Q000097:blood; D001161:Arteriosclerosis / Q000097:blood; D001249:Asthma / Q000097:blood; D003920:Diabetes Mellitus / Q000097:blood; D006801:Humans; D007674:Kidney Diseases / Q000097:blood; D008074:Lipoproteins / Q000378:metabolism*; D010741:Phospholipases A / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D014652:Vascular Diseases / Q000097:blood
D008074:Lipoproteins; D010741:Phospholipases A; D043203:1-Alkyl-2-acetylglycerophosphocholine Esterase