Regulation of Cell Phospholipid Metabolism by Phospholipase A2

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; R o o t E n t r y F VL @ C o m p O b j b W o r d D o c u m e n t G O b j e c t P o o l VL VL 4 @ . / 0 1 2 3 4 5 6 7 8 F Microsoft Word 6.0 Document MSWordDoc Word.Document.6 ; 9507111 Barbour. Phospholipase A2 (PLA2) is a family of enzymes which catalyze the release of fatty acid from phospholipids in cell membranes. Mammalian cells express several structurally diverse isoforms of PLA2. As these enzymes catalyze the same reaction, one must question the purpose of this redundancy. Furthermore, although many studies have provided indirect evidence that PLA2s are important for cell phospholipid metabolism, a lack of specific inhibitors has hampered confirmation of these studies. The goals of this research effort are to provide direct evidence for the roles of the PLA2s in cell phospholipid metabolism and function, and to determine which isoforms of the enzyme are involved in these processes. Antisense RNA will be used to block the expression of each of the three isoforms of PLA2 expressed by the macrophage-like cell line P388D1. Phospholipid composition and phospholipid metabolism will be compared in control cells and cells lacking each of the PLA2s. Functional assays will be performed to determine whether cells that lack the PLA2s retain the capacity to function as m acrophages. Together, these experiments will directly assess the role of PLA2 in phospholipid metabolism and cell function, and provide insight into the need for diverse isoforms of the enzyme. %%% Phospholipase A2 (PLA2) is a family of enzymes which break down a specific group of fats called phospholipids. The goal of this research is to distinguish the function of the various forms of this enzyme in the physiology of cells. This research project involves preparing cells which lack specific forms of PLA2. A mouse cell line, P388D1, was chosen for the experiments because these cells express three types of PHA2. Antisense RNA technology will be used to block the synthesis of each of the PHA2s in P388D1 cells. The antisense cells will be used to distinguish the physiological roles of different forms of PLA2s. *** ; Oh +' 0 $ H l D h S u m m a r y I n f o r m a t i o n ( - R:\WWUSER\TEMPLATE\NORMAL.DOT Panel Summary Shelley A. Graves Shelley A. Graves @ o @ @ UL @ # VL @ d Microsoft Word 6.0 6 ; ; e = e G l l l l l l l 1 # A a T C l l l l l l l l l r 9507111 Barbour. Phospholipase A2 (PLA2) is a family of enzymes which catalyze the release of fatty acid from phospholipids in cell membranes. Mammalian cells express several structurally diverse isoforms of PLA2. As these enzymes catalyze the same reaction, one must question the purpose of this redundancy. Furthermore, although many studies have provided indirect evidence that PLA2s are important for cell phospholipid metabolism, a lack of specific inhibitors has hampered confirmation of these studies. The goals of this research effort are to provide direct evid