LIPID CONTROL IN THE REMOVAL OF DYING BRAIN TUMOR CELLS

描述：细胞凋亡（或程序性细胞死亡）并不完全 申请人的小组已经表明，恶性肿瘤中的细胞凋亡 神经元HN 2 -5细胞系与饱和脂肪酸增加相关 增加膜刚性的酸性磷脂， 5-羟色胺1A受体（5-HT 1A-R）。 申请人假定， 膜脂组成的变化抑制了膜结合酶， 氨基磷脂移位酶（APTL），有助于定位 磷脂酰丝氨酸（PS）的内膜小叶。 的再分配 在细胞凋亡过程中，外叶的PS似乎是一个显性信号， 引发小胶质细胞对凋亡细胞的吞噬作用。 的总目标 该程序是1）了解膜脂组成的变化 发生在HN 2 -5细胞凋亡过程中，2）以确定这些变化 影响TH小胶质细胞对凋亡细胞的吞噬作用。 申请人 提出的研究要么模拟磷脂膜的变化， 以可控的方式复制它们。 他也会试图诱导一些 磷脂的变化，同时保持肿瘤的活力， 细胞 这个项目将有助于提供一个理解的一些 细胞凋亡过程中发生的细胞膜改变。

DESCRIPTION: Apoptosis (or programmed cell death) is not completely understood The applicant's group has shown that apoptosis in the malignant neuronal HN2-5 cell line is associated with an increase in saturated fatty acid- phospholipid which increase membrane rigidity and with the expression of serotonin 1A receptor (5-HT1A -R). The applicant postulates that a change in membrane lipid composition inhibits such membrane-bound enzymes as aminophospholipid translocase (APTL) which helps to localize phosphatidylserine (PS) to the inne membrane leaflet. The redistribution of PS to the outer leaflet during apoptosis appears to be a dominant signal to trigger phagocytosis of apoptotic cells by microglia. The overall goals of this program are 1) to understand wha changes in membrane lipid composition occur in HN2-5 cells during apoptosis an 2) to determine how these changes affect phagocytosis of apoptotic cells by th microglia. The applicant proposes studies that will either mimic the phospholipid membrane changes or reproduce them in a controlled manner. He wil also attempt to induce some of the phospholipid changes while maintaining the viability of the tumor cells. This project will help provide an understanding of some of the membrane alterations that occur during apoptosis.