AGING MODULATES CALCIUM-DEPENDENT PHOSPHATIDYLINOSITOL DEGRADATION BYCEREBRAL-CORTEX SYNAPTIC PLASMA-MEMBRANE PHOSPHOLIPASES

The synaptic plasma membrane (SPM) and cytosol fractions from cerebral cortex of adult (4-mo-old) and aged (27-mo-old) rats were used as a s ource of phospholipase A2 (PLA2) and phospholipase C (PLC). The activi ty of PLC acting on [H-3-inositol]phosphatidylinositol ([H-3]PtdIns) w as investigated in the presence of endogenous and 2 mM Ca2+. Arachidon ic acid (AA) release was studied in the same conditions, using royl-[2 -C-14]arachidonyl-sn-glycerophosphoinositol ([C-14]PtdIns) as a substr ate. In the presence of endogenous Ca2+ (i.e., no added Ca2+) SPM-boun d PLC and PLA2 or diacylglycerol (DAG) lipase of aged brain exert sign ificantly higher activity in degradation of PtdIns as compared to thei r activities in adult brain. Moreover, these enzymes of aged brain are less or not further activated by 2 mM Ca2+, contrary to the enzymes i solated from adult brain. The activity of cytosolic enzymes involved i n degradation [H-3]PtdIns and [C-14]PtdIns and their regulation by Ca2 + ions are not significantly changed in senescent cerebral cortex as c ompared to the adult. The intracellular calcium concentration ([Ca2+]i ), measured with fura-2, is lower in aged brain compared to adult brai n, which may suggest the modification in Ca2+ ion redistribution in ag ed brain and probably its higher concentration in membranes These resu lts indicate that aging modifies significantly the activity of membran e-bound, Ca2+-dependent phospholipase(s) degrading PtdIns, which may b e connected with alteration of Ca2+ ion redistribution and may influen ce the formation and accumulation of very potent lipid messengers as d iacylglycerol, lysophospholipid, and arachidonic acid, known to be inv olved in neurotransmission processes.