FLUID SHEAR-STRESS STIMULATES MEMBRANE PHOSPHOLIPID-METABOLISM IN CULTURED HUMAN ENDOTHELIAL-CELLS
FLUID SHEAR-STRESS STIMULATES MEMBRANE PHOSPHOLIPID-METABOLISM IN CULTURED HUMAN ENDOTHELIAL-CELLS
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DOI：
10.1159/000158963
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发表时间：
1992-11-01
影响因子：
1.7
通讯作者：
FRANGOS, JA
中科院分区：
文献类型：
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作者：
BHAGYALAKSHMI, A;BERTHIAUME, F;FRANGOS, JA
有证据表明，流体剪切力激活了内皮细胞的磷脂转换，但目前尚不清楚哪些磷脂参与了血流信号的转导。将培养的人脐静脉内皮细胞预先标记[C-14]-花生四烯酸，在0.4、1.4和22dyn/cm2的层流切应力下作用30min，然后测定磷脂中放射性的分布。我们观察到在10-30 S时，标记的磷脂酰肌醇、磷脂酰乙醇胺和磷脂酸减少，标记的二酰甘油(DG)和游离的花生四烯酸增加，同时1，4，5-三磷酸(IP_3)水平升高。IP3水平在切变开始后10min出现第二个峰值。这与激动剂刺激的内皮细胞形成对比，在刺激后几分钟内，IP3水平就会恢复到初始值。在有或没有ATP和血清的情况下，血流诱导的IP3反应是相同的。这些结果与切应力对磷脂酶C、磷脂酶A2和DG脂肪酶的激活作用一致。这表明几种磷脂参与了游离花生四烯酸和DG的产生，这两种物质可能是剪应力信号的重要中介。此外，血流可能会导致血管内皮细胞代谢的慢性刺激。
There is evidence suggesting that fluid shear stress activates phospholipid turnover in endothelial cells, but it is not clear which phospholipids are involved in the transduction of the flow signal. Cultured human umbilical-vein endothelial cells were prelabeled with [C-14]-arachidonic acid and subjected to laminar shear stresses of 0.4, 1.4 and 22 dyn/cm2 for times up to 30 min, after which the distribution of the radioactivity in the phospholipids was determined. We observed decreases in labeled phosphatidylinositol, phosphatidylethanolamine and phosphatidic acid at 10-30 s, and increases in labeled diacylglycerol (DG) and free arachidonate, as well as a simultaneous elevation in inositol 1,4,5-triphosphate (IP3) levels. A second peak in IP3 levels was observed 10 min after the onset of shear. This is in contrast with agonist-stimulated endothelial cells, where IP3 levels go back to initial values within a few minutes after stimulation. The flow-induced IP3 response was the same in the presence or absence of ATP and serum in the perfusing medium. These results are consistent with the activation of phospholipase C, phospholipase A2 and DG lipase by shear stress. This suggests that several phospholipids are involved in the production of free arachidonic acid and DG, which are likely to be important mediators of the shear stress signal. In addition, flow may lead to a chronic stimulation of endothelial-cell metabolism.