THE EFFECT OF AGE ON PHOSPHATIDYLINOSITOL KINASE, PHOSPHATIDYLINOSITOL PHOSPHATE KINASE AND DIACYLGLYCEROL KINASE-ACTIVITIES IN RAT-BRAIN CORTEX

A previous study, in which a lysed fraction was used with endogenous p hospholipids as substrate, revealed age-related-changes in PA and PIP2 formation but not in PIP formation (Bothmer et al., Neurochem. Int. 2 1, 223-228, 1992). To rule out the influence of substrate availability in the present study, the effect of age on PI kinase, PIP kinase and DAG kinase activities was studied with exogenous phospholipids as subs trate in the cerebral cortex from 8-month-old, 14-month-old and 26-mon th-old Brown Norway rats. PI kinase activity was predominantly located in a tight membrane-bound protein fraction, DAG kinase activity in cy tosolic and loosely membrane-bound protein fractions, and PIP kinase a ctivity was present in all three protein preparations. The effects of age were limited to a small increase in,kinase activity in the tight m embrane-bound protein fraction in 14-month-old and 26-month-old rats c ompared to 8-month-old rats, and a 10% decrease in PIP kinase activity in the cytosolic protein fraction in 14-month-old and 26-month-old ra ts compared to 8-month-old rats. DAG kinase activity showed no age-rel ated changes. In conclusion, one should take care in comparing rat agi ng with human aging as PI kinase activity shows an age-related decline in human brain cortex (Jolles et al., J. Neurochem. 58, 2326-2329, 19 92). Furthermore, previously reported decreases in PA formation rates in rat brain are probably not due to changes in DAG kinase itself but; to changes in DAG availability, although further experimental evidenc e is needed to confirm this conclusion.