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Biology of Reproduction 64, 339-344 (2001)
© 2001 Society for the Study of Reproduction, Inc.

Regular Article

Platelet-Activating Factor Acetylhydrolase Isoforms I and II in Human Uterus. Comparisons with Pregnant Uterus and Myoma1

Katsuhiko Yasuda2,a, Tadayoshi Okumurab, Hidetaka Okadaa, Tatsuya Nakajimaa, Junkei Aokic, Hiroyuki Araic, Keizo Inouec, Mikio Nishizawab, Seiji Itob, and Hideharu Kanzakia

a Department of Obstetrics and Gynecology, b Department of Medical Chemistry, Kansai Medical University, Osaka 570-0074, Japan c Graduate School of Pharmaceutical Science, The University of Tokyo, Tokyo 113-8657, Japan

ABSTRACT

The concentrations of platelet-activating factor (PAF) that possesses the ability to stimulate myometrial contraction are partially regulated by intracellular type of platelet-activating factor acetylhydrolase (PAF-AH) in many tissues. Tissue cytosol contains at least two intracellular PAF-AH, isoforms I and II. To examine the relationship between the activity and isoforms of intracellular PAF-AH in human uterine myometrium and myoma, we assayed the PAF-AH activity and identified the PAF-AH isoforms I and II by Western blot analysis. The intense bands of the {alpha}2 and ß subunits of PAF-AH isoform I were detected in nonpregnant uterus; however, the specific bands of the {alpha}1 subunit of PAF-AH isoform I and the PAF-AH isoform II were extremely weak. The levels of the {alpha}2 and ß subunits and PAF-AH activity in pregnant uterus (37–39 wk gestation) were significantly lower than those in nonpregnant uterus. On the other hand, the level of ß subunit and the PAF-AH activity in myoma were significantly higher than those in nonpregnant uterus. No significant difference was found in the expression of the PAF-AH isoform II among three tissues. These results indicate that the change in the PAF-AH activity observed in pregnant uterus and myoma are due to the lower or higher protein expression of the PAF-AH isoform I, especially the {alpha}2 and/or ß subunits. The decrease of the uterine PAF-AH activity in the late stage of pregnancy may facilitate the action of PAF to stimulate myometrial contraction.

parturition, pregnancy, uterus

INTRODUCTION

Platelet-activating factor (PAF) was discovered as a chemical mediator released from sensitized basophils [1]. Its structure was elucidated as 1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine [2, 3]. Subsequent studies have demonstrated that PAF is produced upon appropriate stimulation by a variety of human cells, including neutrophils, eosinophils, monocytes, and endothelial cells, and that PAF is related to allergy and inflammation [4, 5]. Platelet-activating factor is also found in the normal brain [6], stomach [7], kidney [8], and uterus [9], in which it may play a physiological role. Platelet-activating factor is considered to be involved in a variety of reproductive processes, including fertilization [10], implantation [11], and parturition [12]. The role of PAF in parturition is not fully defined, but it is well documented that PAF induces myometrial contraction [13] and promotes the synthesis of prostaglandin E2 [14]. Furthermore, we recently reported that concentrations of uterine PAF increased in pregnant rats during the late stages of pregnancy [15].

Platelet-activating factor is inactivated by a specific enzyme, PAF acetylhydrolase (PAF-AH) that removes the acetyl moiety at the sn-2 position of the glycerol backbone [16]. Platelet-activating factor-AH is classified into plasma (extracellular) and tissue (intracellular) types. Plasma type is a 43-kDa monomeric enzyme that abolishes the inflammatory effects of PAF on leukocytes and vasculature, indicating that it is involved in maintaining plasma PAF at certain levels [17]. Recently, purifying and cloning of intracellular PAF-AH was successful. Tissue cytosol contains at least two types of intracellular PAF-AH, isoforms I and II [18]. Isoform II is a 40-kDa monomer, and the amino acid sequence exhibits 41% identity with that of plasma-type PAF-AH [17, 19, 20]. On the other hand, isoform I is classified as isoforms Ia and Ib. Isoform Ia is a heterodimeric enzyme composed of {alpha}1 and {alpha}2 subunits, and isoform Ib is a heterotrimeric enzyme consisting of {alpha}1, {alpha}2, and ß subunits [18]. Complementary DNAs for {alpha}1, {alpha}2, and ß subunits have been cloned from cow [21, 22], human [23, 24], mouse [25], and rat [26]. The homology of the amino acid sequences of each subunit was extremely high among the above mammalian species. The sequence identities of the {alpha}1 subunit are lower than those of the {alpha}2 and ß subunits but are more than 95% among these four species. The expression of the {alpha}1 subunit in rat tissues is fairly low, except the brain and the {alpha}2 subunit were not detected in skeletal muscle and heart [26]. The {alpha}1 subunit and {alpha}2 subunit are 29 kDa and 30 kDa on SDS-PAGE, respectively, and these subunits show about 60% amino acid homology with each other, and both subunits have a catalytic site [21, 22]. The ß subunit (45 kDa), which does not possess enzymatic activity and is considered to have a regulatory site, belongs to the family of WD 40 repeat-containing polypeptides that are typically found as subunits of multimeric protein complexes and may mediate protein-protein interactions. The ß subunit has been identified as a product of the LIS-1 gene, causative gene for Miller-Dieker lissencephaly, which is a brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration [27]. As mentioned before, we found that the activity of intracellular PAF-AH in rat uterine myometrium decreased and the level of PAF increased in later stages of pregnancy [15]. It suggested that the concentrations of PAF to induce the myometrial contraction were, in part, regulated by intracellular PAF-AH. In this study, we have examined the relationship between the activity and protein expression in intracellular PAF-AH isoforms that inactivates PAF to possess the ability to stimulate uterine contraction in nonpregnant and pregnant myometrium. Additionally, we have evaluated PAF-AH activity and PAF-AH isoforms in abnormal myometrial tissues, myomas.

MATERIALS AND METHODS

Chemicals

All electrophoretic reagents were of the highest grade available and were obtained from Bio-Rad Laboratories, Inc. (Richmond, CA). Secondary antibodies were goat anti-rabbit IgG (Biosource, Camarillo, CA)/sheep anti-mouse IgG (Amersham International, Buckinghamshire, UK) linked to horseradish peroxidase. 1-O-Hexadecyl-2-[3H]acetyl-sn-glycero-3-phosphocholine ([3H]PAF, 10 Ci/mmol, 1 Ci = 37 GBq) was purchased from New England Nuclear (Boston, MA). Nonradiolabeled PAF was obtained from Bachem Feinchemikalien AG (Bubendorf, Switzerland).

Selection of Patients and Tissue Collection

Tissue samples were obtained from the patients undergoing myomectomy, hysterectomy, and elective cesarean section. This study was approved by the university ethics committee. Written informed consent was obtained from each patient. Pregnant women (22–31 yr of age) underwent elective lower segment cesarean section for previous cesarean section or breech presentation at 37–39 wk gestation. Regular uterine contractions were not recognized by external monitoring, and they did not complain about onset of labor before the operation. Additionally, they did not receive any drugs that influence uterine contractile ability, such as indomethacin or ß2 adrenoceptor stimulants. Routine cesarean section was carried out under epidural anesthesia or spinal anesthesia. After delivery of the infant and placenta, a 1- to 2-cm sample of myometrium was taken from the upper margin of the lower uterine segment incision using tissue forceps and scissors. Nonpregnant women (34–50 yr of age) underwent total abdominal hysterectomy for endometriosis, myoma, cervical cancer (early stage), endometrial cancer, and ovarian tumor, and the myometrium was taken at the junction of inner cervical os and uterine corpus. In addition, a sample of myoma was obtained from nonpregnant women (30–50 yr of age) undergoing hysterectomy or myomectomy, and the pathologic findings revealed leiomyoma. All samples were snap-frozen in liquid nitrogen and stored at -80°C until homogenizing.

Preparation of Tissue Homogenates

All procedures were performed at 4°C. The uterine myometrium and the myoma (0.5–2 g, respectively) were homogenized in 6 vol of 0.25 M sucrose containing 10 mM Tris-HCl (pH 7.4) with a PT-K/PCU-11 Polytron (Littau, Luzen, Switzerland) homogenizer. This homogenate was centrifuged at 600 x g for 10 min to remove tissue debris, 18 000 x g for 15 min to separate the mitochondrial fraction, and then at 105 000 x g for 60 min to separate microsome fraction. The cytosolic fraction obtained was employed as the source of tissue (intracellular) PAF-AH. The protein concentration was determined by the method of Lowry et al. [28].

Western Blot Analysis of Intracellular PAF-AH

Proteins (40 µg) of the cytosolic fraction from tissue homogenates were solubilized in sample buffer (125 mM Tris-HCl buffer, pH 6.8, containing 5% glycerol, 2% SDS, and 1% 2-mercaptoethanol). In this study, cytosolic fractions of rat fetal brain (21 days of pregnancy) and rat adult kidney (10 wk of age) were employed as a positive control. Sodium dodecylsulfate-PAGE was carried out on a 12.5% polyacrylamide gel for 60–70 min at 30 mA and then electrotransferred onto a polyvinylidenedifluoride (PVDF; Bio-Rad, Hercules, CA) at 15 V for 2 h. The PVDF blots were blocked with blocking buffer (10 mM Tris-HCl buffer, pH 7.4 containing 100 mM NaCl, 0.1% Triton X-100, and 5% skim milk) for 60 min at room temperature. Antibodies against the subunits of PAF-AH isoform I were prepared as reported previously [29]. Antibody against the PAF-AH isoform II was prepared as follows: Balb/c mice were immunized with recombinant human PAF-AH II protein [20], and monoclonal antibodies were produced using the PAI myeloma cell line. One monoclonal antibody producing a hybridoma cell line (clone 10, mouse IgG1) was established. The monoclonal antibody (clone 10) reacts with recombinant PAF-AH isoform II proteins from human, pig, rat, and mouse by Western blot analysis (data not shown). Rabbit polyclonal antibody against the {alpha}1 subunit of PAF AH isoform I was used at a 1:600 dilution in the above bocking buffer. Rabbit polyclonal antibody against the {alpha}2 subunit of PAF AH isoform I was used at a 1:300 dilution. Mouse monoclonal antibody against the ß subunit of PAF-AH isoform I was used at a 1:1000 dilution. The clone culture supernatant including mouse monoclonal antibody against PAF-AH isoform II was used at a 1:2 dilution. The PVDF blots were incubated overnight at 4°C with the indicated antibodies and then washed with a wash solution (10 mM Tris-HCl buffer, pH 7.4 containing 0.1% Triton-X and 100 mM NaCl). The PVDF blots were then incubated with horseradish peroxidase-conjugated secondary antibodies in the wash solution for 1 h and washed with the wash solution; the color was developed using an ECL coloring kit (Amersham, Pharmacia Biotech, Buckinghamshire, UK). The intensities on immunoreactive staining were measured using a scanning densitometer (Advantec Digital Densitirol DMU-33C, Tokyo, Japan).

Platelet-Activating Factor-AH Assay

The activity of PAF-AH in the cytosolic fraction was assayed according to the method of Miwa et al. [30] with minor modifications. Approximately 200–300 µg protein was employed in each PAF-AH assay. Briefly, the assay mixture contained Tris-HCl (30 mM, pH 7.4), BSA (1.2 mg/ml), PAF (0.05 mM, 4 Ci/mol), and cytosol fraction. The final volume was 0.5 ml. The assay mixture was incubated for 30 min at 37°C. The reaction was terminated by the addition of 0.5 ml of 14% trichloroacetic acid. The mixture was centrifuged for 10 min at 4°C (600 x g), and [3H]acetyl-PAF was precipitated out. A volume of 0.1 ml of the supernatant containing [3H]acetate was removed and mixed with 5 ml of scintillation fluid (New England Nuclear, Boston, MA). The water-soluble [3H]acetate released from [3H]acetyl-PAF was then assayed by liquid scintillation spectroscopy. A standard sample of human plasma was assayed with each assay group. No significant change in the standards was noted throughout the study.

Statistical Analysis

Results are expressed as the means ± SEM. Statistical significance was analyzed by one-way ANOVA and post-hoc t-test with StatView 4.5 (Abacus Concepts, Berkeley, CA), and P < 0.05 was considered to be statistically significant.

RESULTS

Western Blot Analysis

Western blot images described in Figure 1 are representative of the results obtained from each of the specific antibodies used in this investigation. As positive controls, immunoblotting with the specific antibodies against {alpha}1, {alpha}2, and ß subunits of PAF-AH isoform I detected intense bands at 29, 30, and 45 kDa, respectively, in rat fetal brain (Fig. 1, A, B, and C, lane 7) as described previously [29]. Similar bands were also detected in rat adult kidney except for a negligible band at 29 kDa, corresponding to the {alpha}1 subunit of PAF-AH isoform I. Instead, we found two molecular masses between 20–25 kDa (Fig. 1A, lane 8) that may represent another isoform or result from proteolytic break down. The specific band of {alpha}1 subunit was extremely weak in human nonpregnant uterine myometrium (Fig. 1A, lanes 1–3), pregnant uterine myometrium (Fig. 1A, lanes 4–6), and myoma (Fig. 1A, lanes 9–11) compared with that observed in rat fetal brain as positive control (Fig. 1A, lane 7). The relative intensity could not be evaluated because the specific band of the {alpha}1 subunit in three tissues was too weak to measure the density.



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  		FIG. 1. Western blot analysis of the intracellular PAF-AH isoform I in nonpregnant and pregnant uterine myometrium and myoma: 40 µg of protein from each cytosolic fraction was resolved by SDS-PAGE and subsequent immunoblotting with specific antibodies. A) The {alpha}1 subunit of PAF-AH isoform I. B) The {alpha}2 subunit of PAF-AH isoform I. C) The ß subunit of PAF-AH isoform I. Lanes 1–3, nonpregnant uterine myometrium; lanes 4–6, pregnant uterine myometrium (37–39 wk gestation); lane 7, rat fetal brain (21 days of pregnancy); lane 8, rat adult kidney (10 wk old); lanes 9–11, myoma

The specific band of {alpha}2 subunit detected in nonpregnant uterine myometrium (Fig. 1B, lanes 1–3) was markedly reduced in pregnant uterine myometriun (Fig. 1B, lanes 4–6). Quantification by scanning densitometry of the {alpha}2 subunit of PAF-AH isoform I are represented graphically (Fig. 2). The relative intensity of the {alpha}2 subunit protein at 30 kDa in pregnant uterine myometrium significantly decreased compared with that in nonpregnant uterine myometrium (0.245 ± 0.055 vs. 1.024 ± 0.055, P < 0.01). However, no significant difference was found between nonpregnant uterine myometrium and myoma.



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  		FIG. 2. Relative protein intensity of the {alpha}2 subunit of PAF-AH isoform I in nonpregnant and pregnant uterine myometrium and myoma. The immunodetected band was quantified by scanning densitometric analysis. Data are expressed as means ± SEM. Numbers of samples used are 14 (nonpregnant uterine myometrium), 15 (pregnant uterine myometrium), and 11 (myoma)

The specific ß subunit band was also detected in human nonpregnant uterine myometrium (Fig. 1C, lanes 1–3). As shown in Figure 3, quantification analysis revealed that the ß subunit protein at 45 kDa was significantly decreased in pregnant uterine myometrium compared with that in nonpregnant uterine myometrium (0.575 ± 0.054 vs. 1.00 ± 0.068, P < 0.01). On the other hand, the relative intensity of the ß subunit protein in myoma was significantly higher than that in the nonpregnant uterine myometrium (1.297 ± 0.093 vs. 1.00 ± 0.068, P < 0.05).



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  		FIG. 3. Relative protein intensity of the ß subunit PAF-AH isoform I in nonpregnant and pregnant uterine myometrium and myoma. Immunodetected band was quantified by scanning densitometric analysis. Data are expressed as means ± SEM. Numbers of samples are the same as in Figure 2

Immunoblotting with the specific antibody against of PAF-AH isoform II detected a distinct band at 40 kDa in rat fetal brain and adult kidney (Fig. 4, lanes 7 and 8, respectively). However, the specific band of PAF-AH isoform II was weak in human nonpregnant uterine myometriun (lanes 1–3), pregnant uterine myometrium (lanes 4–6), and myoma (lanes 9–11) compared with that in rat fetal brain and adult kidney. And quantification by scanning densitometry did not reveal significant differences among those tissues (Fig. 5).



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  		FIG. 4. Western blot analysis of intracellular PAF-AH isoform II in nonpregnant and pregnant uterine myometrium and myoma: 40 µg of protein for each cytosolic fraction was resolved by SDS-PAGE and subsequent immunoblotting with specific antibody. Lanes 1–3, nonpregnant uterine myometrium; lanes 4–6, pregnant uterine myometrium (37–39 wk gestation); lane 7, rat fetal brain (21 days of pregnancy); lane 8, rat adult kidney (10 wk old); lanes 9–11, myoma



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  		FIG. 5. Relative protein intensity of PAF-AH isoform II in nonpregnant and pregnant uterine myometrium and myoma. Immunodetected band was quantified by scanning densitometric analysis. Data are expressed as means ± SEM. Numbers of samples are the same as in Figure 2

Platelet-Activating Factor-AH Activity

The activity of PAF-AH in the cytosolic fraction obtained from nonpregnant uterine myometrium was 110 ± 8 pmol/min/mg protein (mean ± SEM, n = 14). As shown in Figure 6, the enzyme activity in pregnant uterine myometriun was 73 ± 8 pmol/min/mg protein (n = 15) and was significantly lower than that in nonpregnant uterine myometrium (P < 0.05). In contrast, PAF-AH activity in myoma (221 ± 23 pmol/min/mg protein, n=11) was two times higher than that in nonpregnant uterine myometrium (P < 0.01).



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  		FIG. 6. The activity of PAF-AH in the cytosolic fraction obtained from nonpregnant and pregnant uterine myometrium and myoma. Enzyme activity was assayed as described in Materials and Methods. Data are expressed as means ± SEM. Numbers of samples are the same as in Figure 2

DISCUSSION

Previously, we reported that PAF existed in rat nonpregnant uterus by using a platelet aggregation assay and gas chromatography-mass spectrometry [9]. Subsquently, PAF was found in rabbit, mouse, and human uterus. A role for PAF in parturition was first suggested by the findings that this autacoid increased in the amniotic fluid of women in labor compared to women at a similar gestation age not in labor [31]. Exogenous PAF stimulated the contraction of myometrial strips in human [13] and rat. Additionally, the sensitivity of rat myometrial strips to PAF dramatically increased during the late stages of pregnancy [32]. Platelet-activating factor also stimulates the synthesis of prostaglandin [14] and cytokine production [33, 34], and the prostaglandin and cytokine produced in the feto-maternal compartment also stimulate myometrial contractions and induce labor or preterm labor [35].

The concentrations of PAF in tissues or plasma are governed by the equilibrium between its biosynthesis and degradation. The net synthesis of PAF occurs via the de novo pathway. The remodeling pathway, on the other hand, plays a role in the acute inflammatory process [36, 37]. In the degradation, biologically active PAF is converted to the biologically inactive lyso-PAF by PAF-AH. Several distinct isozymes of PAF-AH exist [38]. Subsequent studies have demonstrated that the cytosol fraction contains at least two types of intracellular PAF-AH, isoforms I and II, and that PAF-AH isoform I consists of three subunits, {alpha}1, {alpha}2, and ß. The {alpha}1 and {alpha}2 subunits are considered to have a catalytic site and the ß subunit to have a regulatory site.

In this study, we first reported the protein expression of the subunits of the PAF-AH isoform I in human nonpregnant and pregnant uterine myometrium and myoma. The intense bands of the {alpha}2 and ß subunits of isoform I were detected in nonpregnant uterine myometrium, whereas the specific band of the {alpha}1 subunit of isoform I was extremely weak compared with that observed in rat fetal brain as a positive control (Fig. 1, A–C, lanes 1–3). These results suggest that the expression of the {alpha}1 subunit of isoform I is fairly low in human uterine myometrium and that isoform I in human uterine myometrium is an enzyme composed of {alpha}2 and ß subunits. As shown in Figures 2 and 3, the relative intensity of the {alpha}2 and ß subunits significantly decreased in pregnant uterine myometrium compared to the nonpregnant one. In contrast, the relative intensity of the ß subunit significantly increased in myoma compared to nonpregnant uterine myometrium, although the {alpha}2 subunit did not increase significantly. In support of this observation, we also found that human pregnant uterus had lower levels of PAF-AH activity than nonpregnant ones and myoma had higher levels of PAF-AH activity than nonpregnant ones, respectively (Fig. 6). However, the decrease in PAF-AH activity in pregnant uterine myometrium was less than the observed change in Western blot analysis. Platelet-activating factor-AH activity decreased by 25% compared with that in nonpregnant uterine myometrium, and the {alpha}2 and ß subunits of PAF-AH isoform I decreased by 75% and 40%, respectively. This discrepancy may be due to the contamination of extracellular PAF-AH (plasma type) in the enzyme assay. Because the extracellular PAF-AH could not be removed completely from the cytosolic fraction obtained from tissue samples, all cytosolic fractions were contaminated with extracellular PAF-AH. In our samples, compared with nonpregnant uterine myometrium, pregnant uterine myometrium contained a lot of blood. On the other hand, the increase in PAF-AH activity in myoma was greater than the observed change in Western blot analysis. Platelet-activating factor-AH activity increased 2-fold over that observed in nonpregnant uterine myometrium, and the ß subunit of PAF-AH isoform I increased 1.3-fold. Compared with nonpregnant uterine myometrium, myoma contained lesser blood in our samples. Therefore, it is difficult to explain that the discrepancy is due to the contamination of extracellular PAF-AH in myoma. However, unknown isoforms of intracellular PAF-AH may exist in myoma or the abnormality in the catalytic site that influences the enzyme assay system may be occurring in PAF-AH isoforms I and II, though Western blot analysis did not reveal abnormal bands.

Our results suggest that the decrease of PAF-AH activity in pregnant uterine myometrium in late stages of pregnancy is due to the lower protein expression of {alpha}2 and ß subunits of PAF-AH isoform I. The decrease of PAF-AH activity may facilitate the action of PAF to induce myometrial contractions and then cause preterm or term labor.

The increase of PAF-AH activity in myoma may be due to the higher protein expression of the ß subunit of PAF-AH isoform I. The high activity of PAF-AH may inhibit the action of PAF in myoma. However, the role of PAF and/or PAF-AH in myoma is still unknown.

ACKNOWLEDGMENTS

The authors thank Ms. Noriko Sugie, Ms. Yumiko Morita, and Ms. Miyuki Imai for editorial assistance.

FOOTNOTES

First decision: 30 May 2000.

1 This work was supported in part by grants from the Japan Smoking Research Foundation and grants in Aid for Scientific Research (no. 10671577) from the Ministry of Education, Science, and Culture of Japan. Back

2 Correspondence: Katsuhiko Yasuda, Department of Obstetrics and Gynecology, Kansai Medical University, 10-15 Fumizono-cho, Moriguchi, Osaka, 570-0074, Japan. FAX: 06 6992 3438; yasuda{at}takii.kmu.ac.jp Back

Accepted: August 31, 2000.

Received: April 20, 2000.

REFERENCES

  1. Benveniste J, Henson PM, Cochrane CG. Leukocyte-dependent histamine release from rabbit platelets: the role of IgE, basophils and platelet-activating factor. J Exp Med 1972; 136:1356–1377.[Abstract]
  2. Demopoulos CA, Pinckard RN, Hanahan DJ. Platelet-activating factor: evidence for 1-O-alkyl-2-acetyl-sn-glyceryl-3-phosphorylcholine as the active component (a new class of lipid chemical mediators). J Biol Chem 1979; 254:9355–9358.[Abstract/Free Full Text]
  3. Benveniste J, Tence M, Varenne P, Bidault J, Boullet C, Polonsky J. Semi-synthese et structure purposee du facteur activant les plaquettes (PAF): PAF-acether, un alkyl ether analogue de la lysophosphatidylcholine. CR Acad Sci [D] 1979; 289:1037–1040.
  4. Hanahan DJ. Platelet-activating factor: a biologically active phosphoglyceride. Annu Rev Biochem 1986; 55:483–509.[CrossRef][Medline]
  5. Braquet P, Touqui L, Shen TY, Vargaftig BB. Perspectives in platelet-activating factor research. Pharmacol Rev 1987; 39:97–146.[Medline]
  6. Tokumura A, Kamiyasu K, Takauchi K, Tsukatani H. Evidence for existence of various homologues and analogues of platelet activating factor in a lipid extract of bovine brain. Biochem Biophys Res Commun 1987; 145:415–425.[CrossRef][Medline]
  7. Sugatani J, Fujimura K, Miwa M, Mizuno T, Sameshima Y, Saito K. Occurrence of platelet-activating factor (PAF) in normal rat stomach and alteration of PAF levels by water immersion. FASEB J 1989; 3:65–70.[Abstract]
  8. Camussi G, Bussolino F, Tetta C. Platelet-activating factor and renal disease. In: Saito K, Hanahan DJ (eds.), Platelet Activating Factor and Disease. Tokyo: International Medical Publishers; 1989: 113–128.
  9. Yasuda K, Satouchi K, Saito K. Platelet-activating factor in normal rat uterus. Biochem Biophys Res Commun 1986; 138:1231–1236.[CrossRef][Medline]
  10. Roudebush WE, Minhas BS, Ricker DD, Palmer TV, Dodson MG, Fortunato SJ. Platelet activating factor enhances in vitro fertilization of rabbit oocytes. Am J Obstet Gynecol 1990; 163:1670–1673.[Medline]
  11. Ryan JP, Spinks NR, O'Neill C, Wales RG. Implantation potential and fetal viability of mouse embryos cultured in media supplemented with platelet-activating factor. J Reprod Fertil 1990; 89:309–315.[Abstract/Free Full Text]
  12. Johnston JM. The function of PAF. The communication between the fetal and maternal compartments during parturition. In: Saito K, Hanahan DJ (eds.), Platelet-Activating Factor and Diseases. Tokyo: International Medical Publishers; 1989: 129–138.
  13. Tetta C, Montrucchio G, Alloati G, Roffinello C, Emanuelli G, Benedetto C, Camussi G, Massobrio M. Platelet-activating factor contracts human myometrium in vitro. Proc Soc Exp Biol Med 1986; 183:376–383.[CrossRef][Medline]
  14. Billah MM, DiRenzo GC, Ban C, Truong CT, Hoffman DR, Anceschi MM, Bleasdale JE, Johnston JM. Platelet-activating factor metabolism in human amnion and the responses of this tissue to extracellular platelet-activating factor. Prostaglandins 1985; 30:841–847.[CrossRef][Medline]
  15. Matsubara T, Yasuda K, Johnston JM, Sanezumi M, Okada H, Matsuoka S, Kanzaki H. Platelet activating factor (PAF) and PAF acetylhydrolase activity in rat uterus and placenta during the late stages of pregnancy. Biol Reprod 1997; 56:885–890.[Abstract]
  16. Stafforini DM, Prescott SM, Zimmerman GA, McIntyre TM. Mammalian platelet-activating factor acetylhydrolases. Biochim Biophys Acta 1996; 1301:161–173.[Medline]
  17. Tjoelker LW, Wilder C, Eberhardt C, Stafforini DM, Dietsch G, Schimpf B, Hooper S, Le TH, Cousens LS, Zimmerman GA, Yamada Y, McIntyre TM, Prescott SM, Gray PW. Anti-inflammatory properties of a platelet activating factor acetylhydrolase. Nature 1995; 374:549–553.[CrossRef][Medline]
  18. Hattori M, Arai H, Inoue K. Purification and characterization of bovine brain platelet-activating factor acetylhydrolase. J Biol Chem 1993; 268:18748–18753.[Abstract/Free Full Text]
  19. Hattori K, Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K. Purification and characterization of platelet-activating factor acetylhydrolase II from bovine liver cytosol. J Biol Chem 1995; 270:22308–22313.[Abstract/Free Full Text]
  20. Hattori K, Adachi H, Matsuzawa A, Yamamoto K, Tsujimoto M, Aoki J, Hattori M, Arai H, Inoue K. cDNA cloning and expression of intracellular platelet-activating factor (PAF) acetylhydrolase II. Its homology with plasma PAF acetylhydrolase. J Biol Chem 1996; 271:33032–33038.[Abstract/Free Full Text]
  21. Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K. The catalytic subunit of bovine brain platelet-activating factor acetylhydrolase is a novel type of serine esterase. J Biol Chem 1994; 269:23150–23155.[Abstract/Free Full Text]
  22. Hattori M, Adachi H, Aoki J, Tsujimoto M, Arai H, Inoue K. Cloning and expression of a cDNA encoding the ß-subunit (30-kDa subunit) of bovine brain platelet-activating factor acetylhydrolase. J Biol Chem 1995; 270:31345–31352.[Abstract/Free Full Text]
  23. Adachi H, Tsujimoto M, Hattori M, Arai H, Inoue K. cDNA cloning of human cytosolic platelet-activating factor acetylhydrolase gamma-subunit and its mRNA expression in human tissues. Biochem Biophys Res Commun 1995; 214:180–187.[CrossRef][Medline]
  24. Adachi H, Tsujimoto M, Hattori M, Arai H, Inoue K. Differential tissue distribution of the beta- and gamma-subunits of human cytosolic platelet-activating factor acetylhydrolase (isoform I). Biochem Biophys Res Commun 1997; 233:10–13.[CrossRef][Medline]
  25. Albrecht U, Abu-Issa R, Ratz B, Hattori M, Aoki J, Arai H, Inoue K, Eichele G. Platelet-activating factor acetylhydrolase expression and activity suggest a link between neuronal migration and platelet-activating factor. Dev Biol 1996; 180:579–593.[CrossRef][Medline]
  26. Watanabe M, Aoki J, Manya H, Arai H, Inoue K. Molecular cloning of cDNAs encoding {alpha}1, {alpha}2, and ß subunits of rat brain platelet-activating factor acetylhydrolase. Biochim Biophys Acta 1997; 1409:73–79.
  27. Hattori M, Adachi H, Tsujimoto M, Arai H, Inoue K. Miller-Dieker lissencephaly gene encodes a subunit of brain platelet-activating factor. Nature 1994; 370:216–218.[CrossRef][Medline]
  28. Lowry OH, Rosebrough NJ, Farr AL, Randall RJ. Protein measurement with the Folin phenol reagent. J Biol Chem 1951; 193:265–275.[Free Full Text]
  29. Manya H, Aoki J, Watanabe M, Adachi T, Asou H, Inoue Y, Arai H, Inoue K. Switching of platelet-activating factor acetylhydrolase catalytic subunits in developing rat brain. J Biol Chem 1998; 273:18567–18572.[Abstract/Free Full Text]
  30. Miwa M, Miyake T, Yamanaka T, Sugatani J, Suzuki Y, Sakat S, Arai Y. Characteristics of serum platelet-activating factor (PAF) acetylhydrolase: correlation between deficiency of serum PAF-AH on respiratory symptoms in asthmatic children. J Clin Invest 1988; 82:1983–1991.
  31. Billah NM, Johnston JM. Identification of phospholipid platelet-activating factor (1-O-alkyl-2-acetyl-sn-glycero-3-phosphocholine) in human amniotic fluid and urine. Biochem Biophys Res Commun 1983; 113:51–58.[CrossRef][Medline]
  32. Kim BK, Ozaki H, Lee SM, Karaki H. Increased sensitivity of rat myometrium to the contractile effect of platelet activating factor before delivery. Br J Pharmacol 1995; 115:1211–1214.[Medline]
  33. Barthelson RA, Potter T, Valone FH. Synergistic increase in IL-1 synthesis by the human monocytic cell line THP-1 treated with PAF and endotoxin. Cell Immunol 1990; 125:142–150.[CrossRef][Medline]
  34. Nasu K, Narahara H, Matsui N, Kawano Y, Tanaka Y, Miyakawa I. Platelet-activating factor stimulates cytokine production by human endometrial cells. Mol Hum Reprod 1999; 15:548–553.
  35. Romero R, Mazor M, Tartakovsky B. Systemic administration of interleukin-1 induces preterm parturition in mice. Am J Obstet Gynecol 1991; 165:969–971.[Medline]
  36. Wykle RL, Malone B, Snyder F. Enzymatic synthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine, a hypotensive and platelet-aggregating lipid. J Biol Chem 1980; 255:10256–10260.[Abstract/Free Full Text]
  37. Renooij W, Snyder F. Biosynthesis of 1-alkyl-2-acetyl-sn-glycero-3-phosphocholine (platelet activating factor and a hypotensive lipid) by cholinephosphotransferase in various rat tissues. Biochim Biophys Acta 1981; 663:545–556.[Medline]
  38. Yanoshita R, Kudo I, Ikizawa K, Chang HW, Kobayashi S, Ohno M, Nojima S, Inoue K. Hydrolysis of platelet activating factor and its methylated analogs by acetylhydrolases. J Biochem 1988; 103:815–819.[Abstract/Free Full Text]




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