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.
