Quantitative analysis of platelet-activating factor in rat brain

Tokumura, Akira; Yotsumoto, Takashi; Hoshikawa, Takefumi; Tanaka, Tamotsu; Tsukatani, Hiroaki

doi:10.1016/0024-3205(92)90089-8

Cited by 11 publications

(7 citation statements)

References 19 publications

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“…The change in PAF-AH activity during brain development might regulate PAF content in neural cells. Consistent with this idea, Tokumura et al (14) have reported that PAF content in the young rat brain is higher than that in the adult brain.…”

supporting

confidence: 65%

“…The present data demonstrating that PAF-AH isoform I can hydrolyze AAGPA as well as PAF raises the possibility that the enzyme may regulate the intracellular PAF level by hydrolyzing not only PAF itself but also an intermediate for the de novo PAF synthesis. More interestingly, it is also possible that AAGPA itself may play a role in the cell as a new type of intracellular lipid messenger (14), the level of which is regulated by PAF-AH isoform I.…”

Section: Discussionmentioning

confidence: 99%

“…3, the ␣ 1 /␣ 2 heterodimer exhibited a substrate specificity similar to the ␣ 1 /␣ 1 homodimer rather than the ␣ 2 /␣ 2 homodimer, suggesting that catalysis by the ␣ 1 subunit dominates in the ␣ 1 /␣ 2 heterodimer. To test this possibility, we performed an active site labeling study using [ 14 (Fig. 4).…”

Section: Expression Of Various Catalytic Complexes In the Sf9mentioning

confidence: 99%

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Biochemical Characterization of Various Catalytic Complexes of the Brain Platelet-activating Factor Acetylhydrolase

Manya

Aoki

Kato

et al. 1999

Journal of Biological Chemistry

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Brain intracellular platelet-activating factor acetylhydrolase (PAF-AH) isoform I is a member of a family of complex enzymes composed of mutually homologous ␣ 1 and ␣ 2 subunits, both of which account for catalytic activity, and the ␤ subunit. We previously demonstrated that the expression of one catalytic subunit, ␣ 1 , is developmentally regulated, resulting in a switching of the catalytic complex from ␣ 1 /␣ 2 to ␣ 2 /␣ 2 during brain development (Manya, H., Aoki, J., Watanabe, M., Adachi, T., Asou, H., Inoue, Y., Arai, H., and Inoue, K. (1998) J. Biol. Chem. 273, 18567-18572). In this study, we explored the biochemical differences in three possible catalytic dimers, ␣ 1 /␣ 1 , ␣ 1 /␣ 2 , and ␣ 2 /␣ 2 . The ␣ 2 /␣ 2 homodimer exhibited different substrate specificity from the ␣ 1 /␣ 1 homodimer and the ␣ 1 /␣ 2 heterodimer, both of which showed similar substrate specificity. The ␣ 2 /␣ 2 homodimer hydrolyzed PAF and 1-O-alkyl-2-acetyl-snglycero-3-phosphorylethanolamine (AAGPE) most efficiently among 1-O-alkyl-2-acetyl-phospholipids. In contrast, both ␣ 1 /␣ 1 and ␣ 1 /␣ 2 hydrolyzed 1-O-alkyl-2-acetyl-sn-glycero-3-phosphoric acid more efficiently than PAF. AAGPE was the poorest substrate for these enzymes. The ␤ subunit bound to all three catalytic dimers but modulated the enzyme activity in a catalytic dimer composition-dependent manner. The ␤ subunit strongly accelerated the enzyme activity of the ␣ 2 /␣ 2 homodimer but rather suppressed the activity of the ␣ 1 /␣ 1 homodimer and had little effect on that of the ␣ 1 /␣ 2 heterodimer. The (His 149 to Arg) mutant ␤, which has been recently identified in isolated lissencephaly sequence patients, lost the ability to either associate with the catalytic complexes or modulate their enzyme activity. The enzyme activity of PAF-AH isoform I may be regulated in multiple ways by switching the composition of the catalytic subunit and by manipulating the ␤ subunit.Brain platelet-activating factor acetylhydrolase (PAF-AH 1 isoform I) was first identified in bovine brain as an oligomeric enzyme consisting of two catalytic ␣ 1 and ␣ 2 subunits and a noncatalytic ␤ subunit (1). The oligomeric brain PAF-AH contains a dimer of two highly homologous catalytic subunits, ␣ 1 and ␣ 2 , that share 63% amino acid sequence identity but are not related to any other known proteins (2, 3). The ␣ 1 and ␣ 2 subunits form a heterodimer in the PAF-AH purified from the bovine brain cortex (1). They can also form a catalytically active homodimer when expressed individually in Escherichia coli (3). Recently, the crystal structure of the ␣ 1 /␣ 1 homodimer was determined (4). Surprisingly, the ␣ 1 subunit has a tertiary fold reminiscent of small GTPases such as p21 ras and harbors a chymotrypsin-like Ser-Asp-His triad in its active site (4). Although the catalytic subunits of PAF acetylhydrolase were first identified as a ␣ 1 /␣ 2 heterodimer from young adult bovine brain (1), recent studies have revealed that the ␣ 2 /␣ 2 homodimers are present in vivo as well (5). We have demonstrated in a pr...

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supporting

confidence: 65%

Section: Discussionmentioning

confidence: 99%

Section: Expression Of Various Catalytic Complexes In the Sf9mentioning

confidence: 99%

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Biochemical Characterization of Various Catalytic Complexes of the Brain Platelet-activating Factor Acetylhydrolase

Manya

Aoki

Kato

et al. 1999

Journal of Biological Chemistry

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“…Alternatively, mass spectrometry (MS) combined with capillary or gas chromatography and negative-ion chemical ionization can detect specific glycerophospholipid species in biological samples includ- ing cerebral spinal fluid and has been used to elucidate the predominant 1-alkyl and 1-acyl PAF subclasses as well as oxidized PAF-likelipidsproducedbyneuralcellsandcerebralendothelia. 16,[25][26][27][28][29] Identification, however, depends upon labor-intensive derivatization of target standards prior to analysis and, as such, is not easily amenable to lipid "discovery". More recently, matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry and electrospray ionization mass spectrometry (ESI-MS) has enabled direct detection and identification of lipid species at the molecular level.…”

mentioning

confidence: 99%

Identification and Quantitation of Changes in the Platelet Activating Factor Family of Glycerophospholipids over the Course of Neuronal Differentiation by High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry

et al. 2007

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Glycerophospholipids are important structural lipids in membranes with changes associated with progressive neurodegenerative disorders such as Alzheimer disease. Synthesis of the platelet activating factor (PAF) glycerophospholipid subclass is implicated in the control of neuronal differentiation and death. In this article, we combine nanoflow HPLC and mass spectrometry to screen, identify, and quantitate changes in glycerophospholipid subspecies, specifically PAF family members, over the course of neuronal differentiation. Furthermore, precursor ion scans for fragments characteristic of PAF phosphocholine family members and the standard additions of PAF subspecies were combined to perform absolute quantitation of PAF lipids in undifferentiated and differentiated PC12 cells. Surprisingly, a marked asymmetry was detected in the two predominant PAF species (C16:0, C18:0) over the course of differentiation. These results describe a new technique for the sensitive analysis of lipids combining nanoflow HPLC, ESI-MS, and precursor ion scan. Limits of detection of as little as 2 pg of PAF and LPC were obtained, and analysis of the lipidome of as little as 70,000 cells was performed on this system. Furthermore, application to the PC12 model identified a quantifiable difference between PAF molecular species produced over the course of neuronal differentiation.

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“…Ο PAF φαίνεται ότι συμμετέχει ενεργά στις μεταβολές του κυτταρικού μεταβολισμού που ακολουθούν τη νευρική διέγερση καθώς, ένα από τα χαρακτηριστικά της τελευταίας είναι η ενεργοποίηση της φωσφολιπάσης Α 2 και η ενίσχυση της παραγωγής αραχιδονικού οξέως και λυσο-PAF 115 . Στον εγκέφαλο του επίμυος, τα χαμηλά βασικά επίπεδα του PAF αυξάνονται ως απάντηση σε ποικίλα φυσιολογικά και παθολογικά ερεθίσματα 116 . Οι σπασμοί που εκλύονται από ηλεκτρικά ερεθίσματα, η εγκεφαλική ισχαιμία και οι παροξυσμοί επιληπτικών σπασμών οδηγούν σε βιοχημικές αλλαγές που αποδίδονται στην αύξηση του PAF 117,118 .…”

Section: κνςunclassified

Διερεύνηση Της Διαμεσολάβησης Του Παράγοντα Ενεργοποίησης Των Αιμοπεταλίων (PAF) Σε Προκλητό Οίδημα Από Ισταμίνη

Καλοκασίδης¹

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Επίδραση της λοραταδίνης, ρουπαταδίνης και του WEB 2086 στην επαγωγή της έκφρασης του γονιδίου του H 1 R από την ισταμίνη ........... 3.6.2 Επίδραση της λοραταδίνης, ρουπαταδίνης και του WEB 2086 στην επαγωγή της έκφρασης του γονιδίου του PAFR από την ισταμίνη ........ 3.6.3 Επίδραση της ρουπαταδίνης και του WEB 2086 στην επαγωγή της έκφρασης γονιδίου της cPLA 2 από την ισταμίνη ..

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Quantitative analysis of platelet-activating factor in rat brain

Cited by 11 publications

References 19 publications

Biochemical Characterization of Various Catalytic Complexes of the Brain Platelet-activating Factor Acetylhydrolase

Biochemical Characterization of Various Catalytic Complexes of the Brain Platelet-activating Factor Acetylhydrolase

Identification and Quantitation of Changes in the Platelet Activating Factor Family of Glycerophospholipids over the Course of Neuronal Differentiation by High-Performance Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry

Διερεύνηση Της Διαμεσολάβησης Του Παράγοντα Ενεργοποίησης Των Αιμοπεταλίων (PAF) Σε Προκλητό Οίδημα Από Ισταμίνη

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