Increase of Ca2+-ATPase activity in the brain microsomes of rats with increasing ages: involvement of protein kinase C.

A possible mechanism of aging-induced increase in brain microsomal Ca2+-adenosine triphosphatase (ATPase) activity of rats was investigated. Calcium content in the brain tissues and Ca2+-ATPase activity in the brain microsomes of aging rats (50 weeks of age) increased significantly as compared with those of young rats (5 weeks of age). Brain microsomal Ca2+-ATPase activity in aging rats was decreased significantly by treatment of ethyleneglycol-bis-(aminoethylether) N,N,N',N'-tetraacetic acid (EGTA) (2.7 mM) or digitonin (10(-3)%), while such decrease was not seen in the enzyme activity of young rats. Microsomal Ca2+-ATPase activity in aging rats was markedly decreased by the presence of staurosporine (10(-8) and 10(-7) M), an inhibitor of protein kinase C, in the enzyme reaction mixture, although the enzyme activity of young rats was not inhibited. Meanwhile, dibucaine (10(-6) and 10(-5) M), an inhibitor of Ca2+/calmodulin-dependent protein kinase, did not have an effect on Ca2+-ATPase activity in the brain microsomes of young and aging rats. The addition of protein kinase C (100 and 200 mU/ml) in the reaction mixture caused a significant increase in brain microsomal Ca2+-ATPase activity of young rats. These results suggest that protein kinase C is partly involved in the elevation of brain microsomal Ca2+-ATPase activity in rats with increasing ages.