Inhibition of phospholipase A(2) as a therapeutic target.
The hydrolysis of cell membrane phospholipids by phospholipase A(2) (PLA(2)) leads to the production of numerous lipid mediators of diverse pathological conditions, mainly inflammatory diseases. These include lysophospholipids and their derivatives, and arachidonic acid and its derivatives (the eicosanoids). Both these groups of mediators are produced predominantly by the secretory PLA(2)s (sPLA(2)s) which hydrolyze the phospholipids of the cell surface membrane. Protection of cell membrane from these 'inflammatory enzymes' can therefore be used for the treatment of inflammatory processes. A prototype of cell-impermeable PLA(2) inhibitors, which protect the cell membrane from different sPLA(2)s without affecting vital phospholipid metabolism, is presented and discussed in the present review.
Yedgar
S
S
Department of Biochemistry, Hebrew University-hadassah Medical School, Jerusalem, Israel.
Lichtenberg
D
D
Schnitzer
E
E
D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000627:therapeutic use; D001095:Arachidonic Acids / Q000037:antagonists & inhibitors / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology; D002463:Cell Membrane Permeability; D003600:Cytosol / Q000201:enzymology; D015777:Eicosanoids / Q000096:biosynthesis; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D006801:Humans; D007249:Inflammation / Q000188:drug therapy* / Q000201:enzymology; D008246:Lysophospholipids / Q000037:antagonists & inhibitors / Q000378:metabolism; D008563:Membrane Lipids / Q000378:metabolism; D010741:Phospholipases A / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010743:Phospholipids / Q000378:metabolism
D000894:Anti-Inflammatory Agents, Non-Steroidal; D001095:Arachidonic Acids; D015777:Eicosanoids; D004791:Enzyme Inhibitors; D008246:Lysophospholipids; D008563:Membrane Lipids; D010743:Phospholipids; D010741:Phospholipases A; D002118:Calcium