Aging modulates calcium-dependent phosphatidylinositol degradation by cerebral 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 source of phospholipase A2 (PLA2) and phospholipase C (PLC). The activity of PLC acting on [3H-inositol]phosphatidylinositol ([3H]PtdIns) was investigated in the presence of endogenous and 2 mM Ca2+. Arachidonic acid (AA) release was studied in the same conditions, using 1-stearoyl-[2-14C]arachidonyl-sn-glycerophosphoinositol ([14C]PtdIns) as a substrate. In the presence of endogenous Ca2+ (i.e., no added Ca2+) SPM-bound PLC and PLA2 or diacylglycerol (DAG) lipase of aged brain exert significantly higher activity in degradation of PtdIns as compared to their activities in adult brain. Moreover, these enzymes of aged brain are less or not further activated by 2 mM Ca2+, contrary to the enzymes isolated from adult brain. The activity of cytosolic enzymes involved in degradation [3H]PtdIns and [14C]PtdIns and their regulation by Ca2+ ions are not significantly changed in senescent cerebral cortex as compared to the adult. The intracellular calcium concentration ([Ca2+]i), measured with fura-2, is lower in aged brain compared to adult brain, which may suggest the modification in Ca2+ ion redistribution in aged brain and probably its higher concentration in membranes. These results indicate that aging modifies significantly the activity of membrane-bound, Ca(2+)-dependent phospholipase(s) degrading PtdIns, which may be connected with alteration of Ca2+ ion redistribution and may influence the formation and accumulation of very potent lipid messengers as diacylglycerol, lysophospholipid, and arachidonic acid, known to be involved in neurotransmission processes.
Strosznajder
J
J
Laboratory of Cellular Signalling, Medical Research Centre Polish Academy of Sciences, Warsaw.
Samochocki
M
M
Wikieł
H
H
Małecki
A
A
D000375:Aging / Q000378:metabolism*; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D002462:Cell Membrane / Q000201:enzymology; D002540:Cerebral Cortex / Q000201:enzymology* / Q000254:growth & development; D003600:Cytosol / Q000201:enzymology; D007295:Inositol Phosphates / Q000378:metabolism; D008297:Male; D010716:Phosphatidylinositols / Q000378:metabolism*; D010741:Phospholipases A / Q000378:metabolism*; D054467:Phospholipases A2; D051381:Rats; D017208:Rats, Wistar; D013570:Synaptic Membranes / Q000201:enzymology*; D013574:Synaptosomes / Q000201:enzymology*; D010738:Type C Phospholipases / Q000378:metabolism*
D007295:Inositol Phosphates; D010716:Phosphatidylinositols; D010741:Phospholipases A; D054467:Phospholipases A2; D010738:Type C Phospholipases; D002118:Calcium