Phospholipase A2 enzymes

Kudo, Ichiro; Murakami, Makoto

doi:10.1016/s0090-6980(02)00020-5

Cited by 674 publications

(709 citation statements)

References 346 publications

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“…To investigate this in platelets, we examined the effects of both tamoxifen and nafoxidin on cPLA 2 -α activity in an in vitro cPLA 2 μM nafoxidin or tamoxifen where present during the assay, the activities were 47.8 ± 3.9 or 49.9 ± 10.0 × 10 3 cpm [1-14 C]-arachidonic acid/mg protein, respectively (data is mean ± range from two experiments performed in duplicates). In summary, these results suggest that nafoxidin and tamoxifen impair CB52-induced arachidonic acid release without inhibiting cPLA 2 -α.…”

Section: Effects Of Anti-estrogens On Cb52-induced Eicosanoid Synthesismentioning

confidence: 99%

“…PLA 2 enzymes are a diverse family consisting of at least 16 different enzymes [2]. The intracellular group IV cytosolic PLA 2 -α (cPLA 2 ) [3,4] has attracted much interest in the biosynthesis of eicosanoids since it preferentially release arachidonic acid from membrane phospholipids.…”

Section: Introductionmentioning

confidence: 99%

“…Phosphorylation of cPLA 2 -α has been reported in several cell types and on several amino acid residues [26,27]. The role of phosphorylation in membrane association of cPLA 2 -α is unclear but is has been demonstrated that phosphorylation events can, at least partially, contribute to cPLA 2 -α activation [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

“…The role of phosphorylation in membrane association of cPLA 2 -α is unclear but is has been demonstrated that phosphorylation events can, at least partially, contribute to cPLA 2 -α activation [27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

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Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Forsell

Olsson

Andersson

et al. 2005

Biochemical Pharmacology

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Polychlorinated biphenyls (PCBs) are stable compounds commonly found in nature as environmental pollutants. PCBs can affect the endocrine function of hormones such as steroid-hormones. Also, PCBs are known to be inducers of arachidonic acid release in various cells. We report, here, the effects of PCBs on eicosanoid formation, arachidonic acid release and cytosolic phospholipase A 2 -α(cPLA 2 -α) activation in human platelets. Ortho-substituted PCBs induced a time and dosedependent release of arachidonic acid and the concomitant formation of 12(S)-hydroxy-5,8-cis-10-trans-14-cis-eicosatetraenoic acid (12-HETE) and 12(S)-hydroxy-5-cis-8,10-transheptadecatrienoic acid (12-HHT) in human platelets. The release of arachidonic acid and the formation of 12-HETE was completely blocked by the cPLA 2 -α inhibitors AACOCF 3 or pyrrolidine-1. PCB-treatment of platelets demonstrated that the cPLA 2 -α protein as well as PLA 2 activity translocated to the membrane fraction, independent of a rise in intracellular Ca 2+ . Furthermore, electrophoretic gel mobility shift analysis of cPLA 2 -α on SDS-PAGE demonstrated a PCB-dependent phosphorylation of cPLA 2 -α. The effects of 17β-estradiol and two structurally unrelated anti-estrogens, nafoxidin and tamoxifen on PCB-induced arachidonic acid release in platelets were also investigated. Both nafoxidin and tamoxifen inhibited PCB-induced arachidonic acid release as well as 12-HETE and 12-HHT formation. Interestingly, platelets incubated with PCBs did not aggregate despite the fact that robust release of arachidonic acid was observed. In summary, these results demonstrate that certain PCBs induce activation of cPLA 2 -α independent of a rise in intracellular calcium and a robust release of arachidonic acid release with resulting eicosanoid formation in human platelets.

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Section: Effects Of Anti-estrogens On Cb52-induced Eicosanoid Synthesismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Forsell

Olsson

Andersson

et al. 2005

Biochemical Pharmacology

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“…The association of LIS1 with microtubule associated proteins is reported to be regulated by phosphorylation (25), and a testis specific splice variant as well as polyadenylation variants have been reported for LIS1 mRNA in mice (26). Although phosphorylation of catalytic Paf-ah alpha subunits have not been reported, other members of the phospholipase A2 family, such as cPLA2 alpha, have been shown to be regulated by phosphorylation (27).…”

Section: Discussionmentioning

confidence: 99%

Novel isoforms of intracellular platelet activating factor acetylhydrolase (PAFAH1b2) in human testis; encoded by alternatively spliced mRNAs

Scott

Olson

Long

et al. 2008

Prostaglandins & Other Lipid Mediators

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Platelet activating factor acetylhydrolase (paf-ah), a potent regulator of platelet activating factor activity, plays an important role in various physiological and pathophysiological functions including development, reproduction, inflammation, hemostasis, and apoptosis. Intracellular paf-ah (paf-ahIb) is composed of a regulatory subunit, Pafah1b1, and two highly conserved but non identical catalytic subunits, Pafah1b2 and Pafah1b3. The present study identifies new splice variants of the Pafah1b2 gene transcript. The splice variants retain exons 1-5 and replace exon 6 with alternative exons derived from genomic sequence 3′ to exon 6. Splice variants encode two proteins with different novel carboxy termini. One of the isoforms is expressed exclusively in testis. These new isoforms of pafah1b2 retain the ability to form higher order complexes while replacing known key catalytic residues, which raises the possibility that they may alter the subunit composition and catalytic function of paf-ah-Ib.

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Natural Products Targeting Clinically Relevant Enzymes of Eicosanoid Biosynthesis Implicated in Inflammation and Cancer

Reddy

Yarla

Ediga

et al. 2017

Natural Products Targeting Clinically Relevant Enzymes

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Phospholipase A2 enzymes

Cited by 674 publications

References 346 publications

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Polychlorinated biphenyls induce arachidonic acid release in human platelets in a tamoxifen sensitive manner via activation of group IVA cytosolic phospholipase A2-α

Novel isoforms of intracellular platelet activating factor acetylhydrolase (PAFAH1b2) in human testis; encoded by alternatively spliced mRNAs

Natural Products Targeting Clinically Relevant Enzymes of Eicosanoid Biosynthesis Implicated in Inflammation and Cancer

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