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PAF acetylhydrolase 2 (PAF-AH2) is a serine-dependent, intracellular-type platelet-activating factor (PAF) acetylhydrolase that is expressed in a variety of tissue and cell types but is most abundant in the liver, kidney, testis, and intestines.1,2,3,4 It contains an N-terminal myristoylation site and can translocate from the cytosol to cellular membranes in response to various stressors including UVB radiation, LPS, or oxidative stress, during which PAF-AH2 localizes to the endoplasmic reticulum and Golgi apparatus.2,5 PAF-AH2 hydrolyzes and inactivates PAF, a phospholipid mediator involved in a variety of biological activities, including inflammation, smooth muscle contraction, and fetal development.2,3,6 It also hydrolyzes phospholipids with short-chain or oxidized fatty acids at the sn-2 position.1,2 PAF-AH2 has demonstrated protective activities in various in vitro and in vivo models of oxidative stress.2,4,5 Overexpression of PAF-AH2 reduces cytotoxicity and apoptosis induced by tert-butylhydroperoxide (t-BuOOH) in CHO-K1 cells.5 Conversely, PAF-AH2-deficient (Pafah2-/-) mouse embryonic fibroblasts (MEFs) are more susceptible to t-BuOOH-induced cell death than wild-type MEFs.4 In addition, Pafah2-/- mice exhibit increased hepatic necrosis compared to wild-type animals in a mouse model of carbon tetrachloride-induced hepatic injury.
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1. Expression, purification and characterization of a human serine-
2. Intracellular platelet-
3. The emerging roles of PAF acetylhydrolase. J. Lipid Res. 50(Suppl), S255-S259 (2009).
4. Protection against oxidative stress-
5. Protection against oxidative stress-
6. cDNA cloning and expression of intracellular platelet-