Age-dependent increases in protein kinase C-alpha beta immunoreactivity and activity in the human brain: Possible in vivo modulatory effects on guanine nucleotide regulatory G(i) proteins

In the postmortem human brain (20 specimens of frontal cortex, Brodmann area 9) the abundance of immunoreactive protein kinase C (PKC-alpha beta) and the activity of PKC (calcium, phosphatidylserine, and phorbol ester-dependent enzymes) were determined to study the effect of aging (range 1 month to 89 years) on this regulatory enzyme. Also, the abundance of immunoreactive G protein subunits (G alpha(i1/2), G alpha(i3), G alpha(0), G alpha(s) and G beta) were assessed in parallel to investigate possible relationships with PKC-alpha beta. The abundance of PKC-alpha beta was positively correlated with aging (r = 0.62, n = 20, P < 0.005). Moreover, PKC activity also showed a significant positive correlation with the age of the subject at death (r = 0.55, n = 14, P < 0.05). Because of the known in vitro modulatory role of PKC-alpha beta on G(i) proteins, the existence of an in vivo effect of brain PKC-alpha beta on various G proteins was assessed through correlation analyses. In the brain of the same subjects, there were significant negative correlations between the immunoreactivity of PKC-alpha beta and the immunoreactivities of G alpha(i1/2) (r = -0.78, n = 13, P < 0.005) and G alpha(i3) (r = -0.58, n = 15, P < 0.005). In the same brains, similar negative, although non-significant, correlations were found between the levels of PKC-alpha beta and those of G alpha(0), G alpha(s) and G beta. The results demonstrate an up-regulation of brain PKC-alpha beta with aging and suggest the existence of a relevant in vivo modulatory role of this regulatory enzyme on inhibitory G(i) proteins in the human brain during the process of aging.