FUNCTIONAL IMPAIRMENT IN PROTEIN-KINASE-C BY RACK1 (RECEPTOR FOR ACTIVATED-C KINASE-1) DEFICIENCY IN AGED RAT-BRAIN CORTEX

Several laboratories have reported a lack of protein kinase C (PKC) ac tivation in response to various stimuli in the brain of aged rats. It has been suggested that changes in lipid membrane composition could be related to this functional deficit. However, recent evidence has indi cated that the translocation of PKC to the different subcellular compa rtments is controlled by protein-protein interactions. Recently, a cla ss of proteins, termed receptors for activated C kinase (RACKs), have been described that bind PKC. The present study was conducted to deter mine whether alterations in RACK1, the best-characterized member of RA CKs, were associated with changes in translocation and expression of P KC. Quantitative immunoblotting revealed that RACK1 content was decrea sed by similar to 50% in aged rat brain cortex, compared with that in adult and middle-aged animals. The levels of calcium-independent PKC d elta and epsilon, interacting with RACK1, and related calcium-independ ent PKC activity were not modified by the aging process. By comparison , phorbol ester-stimulated translocation of this activity and of PKC d elta and epsilon immunoreactivity was absent in cortex from aged anima ls, as well as the translocation of the calcium-dependent PKC beta, al so known to interact with RACK1. These results indicate that a deficit in RACK1 may contribute to the functional impairment in PKC activatio n observed in aged rat brain.