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	Emiko Yoda, Kohmi Rai, Mai Ogawa, Yuki Takakura, Hiroshi Kuwata, Hidenori Suzuki, Yoshihito Nakatani, Makoto Murakami, Shuntaro Hara
Journal	PloS one (PLoS One) Vol. 9 Issue 10 Pg. e109409 ( 2014) ISSN: 1932-6203 [Electronic] United States
PMID	25313821 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Phospholipids Receptors, Purinergic P2Y Serotonin Thromboxane A2 Adenosine Diphosphate Collagen Group VI Phospholipases A2 Calcium
Topics	Adenosine Diphosphate (metabolism) Animals Blood Platelets (metabolism) Calcium (metabolism) Collagen (metabolism) Disease Susceptibility Group VI Phospholipases A2 (deficiency, genetics, metabolism) Mice Mice, Inbred C57BL Mice, Knockout Phospholipids (analysis) Platelet Activation Platelet Aggregation Receptors, Purinergic P2Y (metabolism) Serotonin (metabolism) Signal Transduction Spectrometry, Mass, Electrospray Ionization Thrombosis (metabolism, pathology) Thromboxane A2 (metabolism)

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