Stimulation of erythrocyte ceramide formation by platelet-activating factor
Stimulation of erythrocyte ceramide formation by platelet-activating factor
复制标题
DOI：
10.1242/jcs.01730
复制
发表时间：
2005-03-15
影响因子：
4
通讯作者：
Wieder, T
中科院分区：
文献类型：
--
作者：
Lang, PA;Kempe, DS;Wieder, T
渗透性红细胞收缩导致阳离子通道的激活，随后Ca2+进入，刺激鞘磷脂酶，随后形成神经酰胺。然后，Ca2+和神经酰胺激活一种超燃酶，导致细胞膜磷脂酰丝氨酸不对称的分解。红细胞鞘磷脂酶和磷脂酰丝氨酸暴露激活的介质仍然是未知的。研究表明血小板活化因子（PAF）在高渗细胞收缩时从红细胞中释放出来。实验进一步揭示了PAF受体在红细胞中的存在，并表明PAF在等渗条件下刺激鞘磷脂的分解和红细胞神经酰胺的释放。PAF进一步触发红细胞的细胞收缩（前向散射减少）和磷脂酰丝氨酸暴露（膜联蛋白结合）。通过基因敲除PAF受体、PAF受体拮抗剂ABT491或用尿素抑制鞘磷脂酶，膜联蛋白结合的刺激被减弱。综上所述，PAF激活红细胞鞘磷脂磷脂酶，然后形成的神经酰胺导致磷脂酰丝氨酸暴露后的超燃酶活化。
Osmotic erythrocyte shrinkage leads to activation of cation channels with subsequent Ca2+ entry and stimulates a sphingomyelinase with subsequent formation of ceramide. Ca2+ and ceramide then activate a scramblase leading to breakdown of phosphatidylserine asymmetry of the cell membrane. The mediators accounting for activation of erythrocyte sphingomyelinase and phosphatidylserine exposure remained elusive. The study demonstrates that platelet-activating factor (PAF) is released from erythrocytes upon hyperosmotic cell shrinkage. The experiments further disclose the presence of PAF receptors in erythrocytes and show that PAF stimulates the breakdown of sphingomyelin and the release of ceramide from erythrocytes at isotonic conditions. PAF further triggers cell shrinkage (decrease of forward scatter) and phosphatidylserine exposure (annexin binding) of erythrocytes. The stimulation of annexin-binding is blunted by a genetic knockout of PAF receptors, by the PAF receptor antagonist ABT491 or by inhibition of sphingomyelinase with urea. In conclusion, PAF activates an erythrocyte sphingomyelinase and the then formed ceramide leads to the activation of scramblase with subsequent phosphatidylserine exposure.