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Biomedical subjects

Junken Aoki

Publications and source records attributed to Junken Aoki.

53 records · Page 3Linked to original sources
PubMed2003

Identification of a phosphothionate analogue of lysophosphatidic acid (LPA) as a selective agonist of the LPA3 receptor.

Lysophosphatidic acid (LPA) is a bioactive lysophospholipid mediator that acts through G protein-coupled receptors. Most cell lines in culture express one or more LPA receptors, making it difficult to assign a response to specific LPA receptors. Dissection of the signaling properties of LPA has been hampered by lack of LPA receptor subtype-specific agonists and antagonists. The present study characterizes an ester-linked thiophosphate derivative (1-oleoyl-2-O-methyl-rac-glycerophosphothionate, OMPT) of LPA. OMPT is a functional LPA analogue with potent mitogenic activity in fibroblasts. In contrast to LPA, OMPT does not couple to the pheromone response through the LPA(1) receptor in yeast cells. OMPT induces intracellular calcium increases efficiently in LPA(3) receptor-expressing Sf9 cells but poorly in LPA(2) receptor-expressing cells. Guanosine 5'-O-(3-[(35)S]thio)triphosphate binding assays in mammalian cells showed that LPA exhibits agonistic activity on all three LPA receptor subtypes, whereas OMPT has a potent agonistic effect only on the LPA(3) receptor. In transiently transfected HEK293 cells, OMPT stimulates mitogen-activated protein kinases through the LPA(3) but not the LPA(1) or LPA(2) receptors. Furthermore, OMPT-induced intracellular calcium mobilization in mammalian cells is efficiently inhibited by the LPA(1)/LPA(3) receptor-selective antagonist VPC12249. These results establish that OMPT is an LPA(3)-selective agonist. OMPT binding to the LPA(3) receptor in mammalian cells is sufficient to elicit multiple responses, including activation of G proteins, calcium mobilization, and activation of mitogen-activated protein kinases. Thus OMPT offers a powerful probe for the dissection of LPA signaling events in complex mammalian systems.

3T3 Cells↗
PubMed2003

Targeted disruption of intracellular type I platelet activating factor-acetylhydrolase catalytic subunits causes severe impairment in spermatogenesis.

Intracellular type I platelet activating factor-acetylhydrolase is a phospholipase that consists of a dimer of two homologous catalytic subunits alpha1 and alpha2 as well as LIS1, a product of the causative gene for type I lissencephaly. LIS1 plays an important role in neuronal migration during brain development, but the in vivo function of the catalytic subunits remains unclear. In this study, we generated alpha1- and a2-deficient mice by targeted disruption. alpha1(-/-) mice are indistinguishable from wild-type mice, whereas alpha2(-/-) male mice show a significant reduction in testis size. Double-mutant male mice are sterile because of severe impairment of spermatogenesis. Histological examination revealed marked degeneration at the spermatocyte stage and an increase of apoptotic cells in the seminiferous tubules. The catalytic subunits are expressed at high levels in testis as well as brain in mice. In wild-type mice, alpha2 is expressed in all seminiferous tubule cell types, whereas alpha1 is expressed only in the spermatogonia. This expression pattern parallels the finding that deletion of both subunits induces a marked loss of germ cells at an early spermatogenic stage. We also found that the LIS1 protein levels, but not the mRNA levels, were significantly reduced in alpha2(-/-) and double-mutant mice, suggesting that the catalytic subunits, especially alpha2, are a determinant of LIS1 expression level.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2002

Identification of an intracellular receptor for lysophosphatidic acid (LPA): LPA is a transcellular PPARgamma agonist.

Lysophosphatidic acid (LPA) is a pluripotent lipid mediator acting through plasma membrane-associated LPA(x) receptors that transduce many, but not all, of its effects. We identify peroxisome proliferator-activated receptor gamma (PPARgamma) as an intracellular receptor for LPA. The transcription factor PPARgamma is activated by several lipid ligands, but agonists derived from physiologic signaling pathways are unknown. We show that LPA, but not its precursor phosphatidic acid, displaces the drug rosiglitazone from the ligand-binding pocket of PPARgamma. LPA and novel LPA analogs we made stimulated expression of a PPAR-responsive element reporter and the endogenous PPARgamma-controlled gene CD36, and induced monocyte lipid accumulation from oxidized low-density lipoprotein via the CD36 scavenger receptor. The synthetic LPA analogs were effective PPARgamma agonists, but were poor ones for LPA(1), LPA(2), or LPA(3) receptor transfected cells. Transfection studies in yeast, which lack nuclear hormone and LPA(x) receptors, show that LPA directly activates PPARgamma. A major growth factor of serum is LPA generated by thrombin-activated platelets, and media from activated platelets stimulated PPARgamma function in transfected RAW264.7 macrophages. This function was suppressed by ectopic LPA-acyltransferase expression. LPA is a physiologic PPARgamma ligand, placing PPARgamma in a signaling pathway, and PPARgamma is the first intracellular receptor identified for LPA. Moreover, LPA produced by stimulated plasma platelets activates PPARgamma in nucleated cells.

Animals↗
PubMed2002

SEK1/MKK4-mediated SAPK/JNK signaling participates in embryonic hepatoblast proliferation via a pathway different from NF-kappaB-induced anti-apoptosis.

Mice lacking the stress-signaling kinase SEK1 die from embryonic day 10.5 (E10.5) to E12.5. Although a defect in liver formation is accompanied with the embryonic lethality of sek1(-/-) mice, the mechanism of the liver defect has remained unknown. In the present study, we first produced a monoclonal antibody specifically recognizing murine hepatoblasts for the analysis of liver development and further investigated genetic interaction ofsek1 with tumor necrosis factor-alpha receptor 1 gene (tnfr1) and protooncogene c-jun, which are also responsible for liver formation and cell apoptosis. The defective liver formation in sek1(-/-) embryos was not protected by additionaltnfr1 mutation, which rescues the embryonic lethality of mice lacking NF-kappaB signaling components. There was a progressive increase in the hepatoblast cell numbers of wild-type embryos from E10.5 to E12.5. Instead, impaired hepatoblast proliferation was observed in sek1(-/-) livers from E10.5, though fetal liver-specific gene expression was normal. The impaired phenotype in sek1(-/-) livers was more severe than in c-jun(-/-) embryos, and sek1(-/-) c-jun(-/-) embryos died more rapidly before E8.5. The hepatoblast proliferation required no hematopoiesis, since liver development was not impaired in AML1(-/-) mice that lack hematopoietic functions. Stimulation of stress-activated protein kinase/c-Jun N-terminal kinase by hepatocyte growth factor was attenuated in sek1(-/-) livers. Thus, SEK1 appears to play a crucial role in hepatoblast proliferation and survival in a manner apparently different from NF-kappaB or c-Jun.

Animals↗
PubMed2002

Serum lysophosphatidic acid is produced through diverse phospholipase pathways.

Lysophosphatidic acid (LPA) is a lipid mediator with multiple biological activities that accounts for many biological properties of serum. LPA is thought to be produced during serum formation based on the fact that the LPA level is much higher in serum than in plasma. In this study, to better understand the pathways of LPA synthesis in serum, we evaluated the roles of platelets, plasma, and phospholipases by measuring LPA using a novel enzyme-linked fluorometric assay. First, examination of platelet-depleted rats showed that half of the LPA in serum is produced via a platelet-dependent pathway. However, the amount of LPA released from isolated platelets after they are activated by thrombin or calcium ionophore accounted for only a small part of serum LPA. Most of the platelet-derived LPA was produced in a two-step process: lysophospholipids such as lysophosphatidylcholine (LPC), lysophosphatidylethanolamine, and lysophosphatidylserine, were released from activated rat platelets by the actions of two phospholipases, group IIA secretory phospholipase A(2) (sPLA(2)-IIA) and phosphatidylserine-specific phospholipase A(1) (PS-PLA(1)), which were abundantly expressed in the cells. Then these lysophospholipids were converted to LPA by the action of plasma lysophospholipase D (lysoPLD). Second, accumulation of LPA in incubated plasma was strongly accelerated by the addition of recombinant lysoPLD with a concomitant decrease in LPC accumulation, indicating that the enzyme produces LPA by hydrolyzing LPC produced during the incubation. In addition, incubation of plasma isolated from human subjects who were deficient in lecithin-cholesterol acyltransferase (LCAT) did not result in increases of either LPC or LPA. The present study demonstrates multiple pathways for LPA production in serum and the involvement of several phospholipases, including PS-PLA(1), sPLA(2)-IIA, LCAT, and lysoPLD.

Animals↗
PubMed2002

SREC-II, a new member of the scavenger receptor type F family, trans-interacts with SREC-I through its extracellular domain.

The scavenger receptor expressed by endothelial cells (SREC) with an extremely large cytoplasmic domain, was originally identified in a human endothelial cell line. In this study, we have cloned a second isoform named SREC-II and shown that there is a heterophilic interaction between SREC-I and -II at their extracellular domains. The cDNA for murine SREC-II encodes an 834-amino acid protein with 35% homology to SREC-I. Similar to SREC-I, SREC-II contains multiple epidermal growth factor-like repeats in its extracellular domain. However, in contrast to SREC-I, SREC-II had little activity to internalize modified low density lipoproteins (LDL). A Northern blot analysis revealed a tissue expression pattern of SREC-II similar to that of SREC-I with predominant expression in human heart, lung, ovary, and placenta. Mouse fibroblast L cells with no tendency to associate showed noticeable aggregation when SREC-I was overexpressed in these cells, whereas overexpression of SREC-II caused only slight aggregation. Remarkably, intense aggregation was observed when SREC-I-expressing cells were mixed with those expressing SREC-II. Deletion of almost all of the cytoplasmic receptor domain had no effect on the receptor expression and cell aggregation, indicating that solely the extracellular domain is involved in cell aggregation. The association of SREC-I and -II was effectively suppressed by the presence of scavenger receptor ligands such as acetylated LDL and oxidized LDL. These findings suggest that SREC-I and -II show weak cell-cell interaction by their extracellular domains (termed homophilic trans-interaction) but display strong heterophilic trans-interaction through the extracellular epidermal growth factor-like repeat domains.

Amino Acid Sequence↗
PubMed2002

Lysophosphatidic acid (LPA) receptors are activated differentially by biological fluids: possible role of LPA-binding proteins in activation of LPA receptors.

Lysophosphatidic acid (LPA) exerts multiple biological functions through G protein-coupled receptors (EDG2/LPA(1), EDG4/LPA(2), and EDG7/LPA(3)) and is present in serum where it is associated with albumin. In this study we examined LPA activity in various biological fluids by measuring the LPA-induced increase in the intracellular concentration of calcium ion in three types of Sf9 insect cells, each expressing one of the LPA receptors. Using this system, we found that EDG2 and EDG4, but not EDG7, were activated strongly by addition of incubated plasma. By contrast, LPA detected in seminal plasma, which contains a low concentration of albumin, selectively activated EDG7. After LPA in these samples was extracted and reconstituted, it activated all three receptors. We also found that serum albumin readily inhibits the activation of EDG7 but not the activation of EDG2 or EDG4. In addition, plasma from Nagase analbuminemic rats but not plasma from control Sprague-Dawley rats was found to strongly activate EDG7, although the plasma of these two types of rats contained equal amounts of LPA and activated both EDG2 and EDG4. The present study shows that serum albumin can negatively regulate EDG7 but not EDG2 or EDG4, and suggests that protein factors are present in seminal plasma and deliver LPA efficiently to EDG7 but not to EDG2 or EDG4.

Albumins↗
PubMed2002

Autotaxin has lysophospholipase D activity leading to tumor cell growth and motility by lysophosphatidic acid production.

Autotaxin (ATX) is a tumor cell motility-stimulating factor, originally isolated from melanoma cell supernatants. ATX had been proposed to mediate its effects through 5'-nucleotide pyrophosphatase and phosphodiesterase activities. However, the ATX substrate mediating the increase in cellular motility remains to be identified. Here, we demonstrated that lysophospholipase D (lysoPLD) purified from fetal bovine serum, which catalyzes the production of the bioactive phospholipid mediator, lysophosphatidic acid (LPA), from lysophosphatidylcholine (LPC), is identical to ATX. The Km value of ATX for LPC was 25-fold lower than that for the synthetic nucleoside substrate, p-nitrophenyl-tri-monophosphate. LPA mediates multiple biological functions including cytoskeletal reorganization, chemotaxis, and cell growth through activation of specific G protein-coupled receptors. Recombinant ATX, particularly in the presence of LPC, dramatically increased chemotaxis and proliferation of multiple different cell lines. Moreover, we demonstrate that several cancer cell lines release significant amounts of LPC, a substrate for ATX, into the culture medium. The demonstration that ATX and lysoPLD are identical suggests that autocrine or paracrine production of LPA contributes to tumor cell motility, survival, and proliferation. It also provides potential novel targets for therapy of pathophysiological states including cancer.

Animals↗
PubMed2002

Nerve growth factor activates mast cells through the collaborative interaction with lysophosphatidylserine expressed on the membrane surface of activated platelets.

Effect of nerve growth factor (NGF) on platelet-associated mast cell activation was investigated. Although neither NGF alone nor platelets alone induced significant 5-hydroxytriptamine (5-HT) release from rat peritoneal mast cells, marked 5-HT release was detected when costimulated with NGF and calcium ionophore-activated platelets. This response reached maximal levels as early as 5 min after the initiation of the coincubation and was completely blocked by anti-NGF Ab or by an inhibitor for a tyrosine kinase of the trkA NGF receptor. Paraformaldehyde-fixed platelets activated with either calcium ionophore or thrombin exhibited the collaborative ability, suggesting the possible involvement of some membrane molecules expressed on activated platelets in mast cell activation. Because activation of platelets induced expression of phosphatidylserine (PS) and/or lysoPS on membrane surface, and since lysoPS, unlike PS, initiated the NGF-induced 5-HT release, lysoPS expressed on activated platelets may be involved in the mast cell activation. Moreover, intradermal injection of NGF and activated platelets into the rat skin increased local vascular permeability. These findings suggested that NGF collaboratively worked with membrane lysoPS of activated platelets to induce mast cell activation. Thus, NGF released in response to inflammatory stimuli may contribute to mast cell activation in collaboration with locally activated platelets in the process of inflammations and tissue repair.

Animals↗
PubMed2002

A novel phosphatidic acid-selective phospholipase A1 that produces lysophosphatidic acid.

Lysophosphatidic acid (LPA) is a lipid mediator with diverse biological properties, although its synthetic pathways have not been completely solved. We report the cloning and characterization of a novel phosphatidic acid (PA)-selective phospholipase A(1) (PLA(1)) that produces 2-acyl-LPA. The PLA(1) was identified in the GenBank(TM) data base as a close homologue of phosphatidylserine (PS)-specific PLA(1) (PS-PLA(1)). When expressed in insect Sf9 cells, this enzyme was recovered from the Triton X-100-insoluble fraction and did not show any catalytic activity toward exogenously added phospholipid substrates. However, culture medium obtained from Sf9 cells expressing the enzyme was found to activate EDG7/LPA(3), a cellular receptor for 2-acyl-LPA. The activation of EDG7 was further enhanced when the cells were treated with phorbol ester or a bacterial phospholipase D, suggesting involvement of phospholipase D in the process. In the latter condition, an increased level of LPA, but not other lysophospholipids, was confirmed by mass spectrometry analyses. Expression of the enzyme is observed in several human tissues such as prostate, testis, ovary, pancreas, and especially platelets. These data show that the enzyme is a membrane-associated PA-selective PLA(1) and suggest that it has a role in LPA production.

Amino Acid Sequence↗
PubMed2002

A therapeutic agent with oriented carbohydrates for treatment of infections by Shiga toxin-producing Escherichia coli O157:H7.

Infection with Shiga toxin (Stx)-producing Escherichia coli O157:H7, which causes diarrhea and hemorrhagic colitis in humans, often results in fatal systemic complications, such as neurological damage and hemolytic-uremic syndrome. Because Stx circulating in the blood is a major causative factor of these complications, the development of a Stx neutralizer that functions in the circulation holds promise as a viable therapy. Here we developed a series of carbosilane dendrimers, in which trisaccharides of globotriaosyl ceramide, a receptor for Stx, were variously oriented at their termini (referred to as SUPER TWIG), and identified a SUPER TWIG with six trisaccharides as a Stx neutralizer functioning in the circulation. This SUPER TWIG specifically bound to Stx with high affinity (K(d) = 1.1 x 10(-6) M) and inhibited the incorporation of the toxin into target cells. Intravenous administration of the SUPER TWIG along with Stx to mice substantially reduced the fatal brain damage and completely suppressed the lethal effect of Stx. Moreover, the SUPER TWIG protected mice from challenge with a fatal dose of E. coli O157:H7, even when administered after the establishment of the infection. The SUPER TWIG neutralized Stx in vivo by a mechanism in which the accumulation and immediate degradation of Stx by phagocytic macrophages present in the reticuloendothelial system were induced. Taken together, our findings indicate that this SUPER TWIG is therapeutic agent against infections by Stx-producing E. coli.

Animals↗
PubMed2002

Structure and function of phosphatidylserine-specific phospholipase A1.

Phospholipase A1 (PLA1) is an enzyme that hydrolyzes the sn-1 fatty acids from phospholipids and produces 2-acyl-lysophospholipids. Although PLA1 activities are detected in many tissues and cell lines, a limited number of PLA1s have been purified and cloned so far. These include phosphatidylserine (PS)-specific PLA1 (PS-PLA1) from rat platelets, PLA1 from vespid venom, and phosphatidic acid (PA)-preferential PLA1 (PA-PLA1). Structurally, the former two PLA1s belong to the lipase family, where they form a subfamily among the lipase family. An alignment of the PLA1s with other members of the lipase family revealed two molecular characteristics of PLA1: the presence of extremely short lids and deleted beta9 loops. The two surface loops have been implicated in the ligand recognition in human pancreatic lipase (PL) and guinea pig PL-related protein 2. Under physiological conditions, accessibility of PS-PLA1 to its substrate is limited as it is a secreted enzyme and PS is normally located in the inner leaflet of the lipid bilayer. However, PS-PLA1 efficiently hydrolyzes PS exposed on the surface of cells such as apoptotic cells and activated platelets, and produces 2-acyl-lysophosphatidylserine (lysoPS), which is a lipid mediator for mast cells, T cells and neural cells. Identification of PS-PLA1 reveals the presence of PLA1 subfamily within the lipase family and suggests that PLA1 has a role in the production of lysophospholipid mediators.

Amino Acid Sequence↗
PubMed2002

A novel phospholipase A1 with sequence homology to a mammalian Sec23p-interacting protein, p125.

p125, a mammalian Sec23p-interacting protein, exhibits sequence homology with bovine testis phosphatidic acid-preferring phospholipase A(1). In this study, we identified and characterized a new homologue of p125, KIAA0725p. KIAA0725p exhibited remarkable sequence similarity with p125 throughout the entire sequence determined but lacked an N-terminal proline-rich, Sec23p-interacting region. In vitro binding analysis showed that KIAA0725p does not bind to Sec23p. KIAA0725p possessed phospholipase A(1) activity preferentially for phosphatidic acid. We examined the effects of overexpression of KIAA0725p on the morphology of organelles. Overexpression of KIAA0725p, like that of p125, caused dispersion of the endoplasmic reticulum-Golgi intermediate compartment and Golgi apparatus. Different from the case of p125, overexpression of KIAA0725p resulted in dispersion of tethering proteins located in the Golgi region and caused aggregation of the endoplasmic reticulum. Our results indicate that KIAA0725p is a new member of the phosphatidic acid-preferring phospholipase A(1) protein family and suggest that the cellular function of KIAA0725p is different from that of p125.

Amino Acid Sequence↗
PubMed2002

Critical role of lysophospholipids in the pathophysiology, diagnosis, and management of ovarian cancer.

Lysophosphatidic acid (LPA), the simplest of all phospholipids, exhibits pleiomorphic functions in multiple cell lineages. The effects of LPA appear to be mediated by binding of LPA to specific members of the endothelial differentiation gene (Edg) family of G protein-coupled receptors (GPCR). Edg 2, Edg4, and Edg7 are high affinity receptors for LPA, and Edg1 may be a low affinity receptor for LPA. PSP24 has been shown to be responsive to LPA in Xenopus oocytes, however, its role in mammalian cells is unclear. The specific biochemical events initiated by the different Edg receptors, as well as the biological outcomes of activation of the individual receptors, are only beginning to be determined. LPA levels are consistently elevated in the plasma and ascites of ovarian cancer patients, but not in most other epithelial tumors, with the exception of cervix and endometrium, suggesting that LPA may be of particular importance in the pathophysiology of ovarian cancer. In support of this concept, ovarian cancer cells constitutively and inducibly produce high levels of LPA and demonstrate markedly different responses to LPA than normal ovarian surface epithelium. Edg4 and Edg7 levels are consistently increased in malignant ovarian epithelial cells contributing to the aberrant response of ovarian cancer cells to LPA. Edg2 may represent a negative regulatory LPA receptor inducing apoptosis in ovarian cancer cells. Thus, increased levels of LPA, altered receptor expression and altered responses to LPA may contribute to the initiation, progression or outcome of ovarian cancer. Over 40% of known drugs target GPCR, making LPA receptors attractive targets for molecular therapeutics. Indeed, using the structure-function relationship of LPA in model systems, we have identified selective Edg2 anatgonists, as well as Edg4 and Edg7 agonists. These lead compounds are being assessed in preclinical model systems. Understanding the mechanisms regulating LPA production, metabolism and function could lead to improved methods for early detection and to new targets for therapy in ovarian cancer.

Biomarkers, Tumor↗
PubMed2002

Identification of platelet-activating factor acetylhydrolase II in human skin.

Platelet-activating factor acetylhydrolases are a family of specialized phospholipase A2 enzymes. They serve an anti-inflammatory function by converting the proinflammatory autocoid, PAF, into biologically inactive lyso-PAF, by the removal of the sn-2 acetyl group of this glycerophospholipid. Similarly, platelet-activating factor acetylhydrolases can also degrade oxidatively modified sn-2 polyunsaturated-fatty-acid-containing phospholipids, which are toxic to cells. Platelet-activating factor acetylhydrolase II is a recently cloned member of this family of specialized phospholipases. Consistent with a potential role of this intracellular enzyme in protecting membrane phospholipids against oxidative stress, platelet-activating factor acetylhydrolase II has been shown to translocate from cytosol to membranes in response to pro-oxidative stressors, and overexpression of this enzyme decreases the cytotoxic effects of these agents. The objective of this study was to assess whether platelet-activating factor acetylhydrolase II is involved in protecting skin against oxidative stress. Platelet-activating factor acetylhydrolase II protein was demonstrated in human skin by immunohistochemistry, with the highest levels of the enzyme found in sebaceous glands and lesser amounts in epidermal keratinocytes. Treatment of epidermal cells with t-butylhydroperoxide or ultraviolet B radiation resulted in platelet-activating factor acetylhydrolase II translocation from cytosol to membranes. To assess the role of this enzyme in epidermal function, a recombinant retroviral strategy was used to overexpress platelet-activating factor acetylhydrolase II in the human keratinocyte-derived cell line HaCaT. Overexpression of platelet-activating factor acetylhydrolase II protected HaCaT cells against apop tosis induced by oxidative stressors t-butylhydroperoxide and ultraviolet B radiation. Similar levels of apoptosis, however, were seen in both control and platelet-activating-factor-acetylhydrolase-II-over expressing HaCaT cells in response to C2 ceramide. These studies demonstrate the presence of platelet-activating factor acetylhydrolase II in a restricted pattern in human skin, and provide evidence that this specialized phospholipase is involved in protecting this organ against oxidative stress through the degradation of oxidatively modified bioactive phospholipids.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗
PubMed2002

Platelet-activating factor acetylhydrolase (PAF-AH).

Platelet-activating factor (PAF) is one of the most potent lipid messengers involved in a variety of physiological events. The acetyl group at the sn-2 position of its glycerol backbone is essential for its biological activity, and its deacetylation induces loss of activity. The deacetylation reaction is catalyzed by PAF-acetylhydrolase (PAF-AH). A series of biochemical and enzymological evaluations revealed that at least three types of PAF-AH exist in mammals, namely the intracellular types I and II and a plasma type. Type I PAF-AH is a G-protein-like complex consisting of two catalytic subunits (alpha1 and alpha2) and a regulatory beta subunit. The beta subunit is a product of the LIS1 gene, mutations of which cause type I lissencephaly. Recent studies indicate that LIS1/beta is important in cellular functions such as induction of nuclear movement and control of microtubule organization. Although substantial evidence is accumulating supporting the idea that the catalytic subunits are also involved in microtubule function, it is still unknown what role PAF plays in the process and whether PAF is an endogenous substrate of this enzyme. Type II PAF-AH is a single polypeptide and shows significant sequence homology with plasma PAF-AH. Type II PAF-AH is myristoylated at the N-terminus and like other N-myristoylated proteins is distributed in both the cytosol and membranes. Plasma PAF-AH is also a single polypeptide and exists in association with plasma lipoproteins. Type II PAF-AH as well as plasma PAF-AH may play a role as a scavenger of oxidized phospholipids which are thought to be involved in diverse pathological processes, including disorganization of membrane structure and PAF-like proinflammatory action. In this review, we will focus on the structures and possible biological functions of intracellular PAF-AHs.

1-Alkyl-2-acetylglycerophosphocholine Esterase↗