title: Group VIB calcium-independent phospholipase A2 (iPLA2γ) regulates platelet activation, hemostasis and thrombosis in mice.
abstract: In platelets, group IVA cytosolic phospholipase A2 (cPLA2α) has been implicated as a key regulator in the hydrolysis of platelet membrane phospholipids, leading to pro-thrombotic thromboxane A2 and anti-thrombotic 12-(S)-hydroxyeicosatetranoic acid production. However, studies using cPLA2α-deficient mice have indicated that other PLA2(s) may also be involved in the hydrolysis of platelet glycerophospholipids. In this study, we found that group VIB Ca2+-independent PLA2 (iPLA2γ)-deficient platelets showed decreases in adenosine diphosphate (ADP)-dependent aggregation and ADP- or collagen-dependent thromboxane A2 production. Electrospray ionization mass spectrometry analysis of platelet phospholipids revealed that fatty acyl compositions of ethanolamine plasmalogen and phosphatidylglycerol were altered in platelets from iPLA2γ-null mice. Furthermore, mice lacking iPLA2γ displayed prolonged bleeding times and were protected against pulmonary thromboembolism. These results suggest that iPLA2γ is an additional, long-sought-after PLA2 that hydrolyzes platelet membranes and facilitates platelet aggregation in response to ADP.
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Emiko
authors.initials: E
authors.lastname: Yoda
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Kohmi
authors.initials: K
authors.lastname: Rai
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ogawa
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Takakura
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kuwata
authors.affiliation: Division of Morphological and Biomolecular Research, Graduate School of Medicine, Nippon Medical School, Bunkyo-ku, Tokyo, Japan.
authors.forename: Hidenori
authors.initials: H
authors.lastname: Suzuki
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Nakatani
authors.affiliation: Lipid Metabolism Project, Tokyo Metropolitan Institute of Medical Science, Setagaya-ku, Tokyo, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murakami
authors.affiliation: Division of Health Chemistry, Department of Healthcare and Regulatory Sciences, School of Pharmacy, Showa University, Shinagawa-ku, Tokyo, Japan.
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
mesh_terms: D000244:Adenosine Diphosphate / Q000378:metabolism; D000818:Animals; D001792:Blood Platelets / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D003094:Collagen / Q000378:metabolism; D004198:Disease Susceptibility; D054522:Group VI Phospholipases A2 / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010743:Phospholipids / Q000032:analysis; D015539:Platelet Activation; D010974:Platelet Aggregation; D058470:Receptors, Purinergic P2Y / Q000378:metabolism; D012701:Serotonin / Q000378:metabolism; D015398:Signal Transduction; D021241:Spectrometry, Mass, Electrospray Ionization; D013927:Thrombosis / Q000378:metabolism / Q000473:pathology; D013928:Thromboxane A2 / Q000378:metabolism
chemical_list: D010743:Phospholipids; D058470:Receptors, Purinergic P2Y; D012701:Serotonin; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D003094:Collagen; D054522:Group VI Phospholipases A2; D002118:Calcium