Evidence for a Role for Phospholipase C, but not Phospholipase A2, in Platelet Activation in Response to Low Concentrations of Collagen

Evidence for a Role for Phospholipase C, but not Phospholipase A2, in Platelet Activation in Response to Low Concentrations of Collagen
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磷脂酶 C(而非磷脂酶 A2)在响应低浓度胶原蛋白的血小板激活中发挥作用的证据

DOI:
10.1055/s-0037-1615763
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发表时间:
2001
影响因子:
6.7
通讯作者:
A. Mcnicol
A. Mcnicol
中科院分区:
医学2区
文献类型:
--
作者:
L. Lockhart;Caroline Pampolina;B. Nickolaychuk;A. Mcnicol

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Summary The release of arachidonic acid is a key component in platelet activation in response to low concentrations (1-20 g/ml) of collagen. The precise mechanism remains elusive although a variety of pathways have been implicated. In the present study the effects of inhibitors of several potentially key enzymes in these pathways have been examined. Collagen (1-10 g/ml) caused maximal platelet aggregation which was accompanied by the release of arachidonic acid, the synthesis of thromboxane A2, and p38MAPK phosphorylation. Preincubation with the dual cyclooxygenase/lipoxygenase inhibitor BW755C inhibited aggregation and thromboxane production, and reduced p38MAPK phosphorylation. A phospholipase C inhibitor, U73122, blocked collagen-induced aggregation and reduced arachidonic acid release, thromboxane synthesis and p38MAPK phosphorylation. Pretreatment with a cytosolic phospholipase A2 inhibitor, AACOCF3, blocked collagen-induced aggregation, reduced the levels of thromboxane formation and p38MAPK phosphorylation but had no significant effect on arachidonic acid release. In contrast inhibition of PKC by Rö31-8220 inhibited collagen-induced aggregation, did not affect p38MAPK phosphorylation but significantly potentiated arachidonic acid release and thromboxane formation. Collagen caused the tyrosine phosphorylation of phospholipase C 2 which was inhibited by pretreatment with U73122, unaffected by AACOCF3 and enhanced by Rö31-8220. These results suggest that cytosolic phospholipase A2 plays no role in the arachidonic acid release in response to collagen. In contrast, the data are consistent with phospholipase C 2 playing a role in an intricately controlled pathway, or multiple pathways, mediating the release of arachidonic acid in collagen-stimulated platelets.
DOI: 10.1042/bj2880925
发表时间: 1992-12
期刊: The Biochemical journal
影响因子: --
作者:
J. Smith;M. Selak;Carol Dangelmaier;J. Daniel
通讯作者: J. Smith;M. Selak;Carol Dangelmaier;J. Daniel
85-kDa 磷脂酶 A2 的紧密结合抑制剂(而非 14-kDa 磷脂酶 A2)可抑制凝血酶刺激的人血小板中游离花生四烯酸的释放。
DOI: --
发表时间: 1994
期刊: The Journal of biological chemistry
影响因子: --
作者:
Bartoli,F;Lin,HK;Ghomashchi,F;Gelb,MH;Jain,MK;Apitz-Castro,R
通讯作者: Apitz-Castro,R