Several laboratories have reported a lack of protein kinase C (PKC) activation 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 indicated that the translocation of PKC to the different subcellular compartments is controlled by protein- protein interactions . Recently, a class of proteins, termed receptors for activated C kinase (RACKS), have been described that bind PKC. The present study was conducted to determine whether alterations in RACK1, the best-characterized member of RACKS, were associated with changes in translocation and expression of PKC. Quantitative immunoblotting revealed that RACK1 content was decreased by -50% in aged rat brain cortex, compared with that in adult and middle-aged animals. The levels of calcium-independent PKC6 and E, interacting with RACK1, and related calcium-independent PKC activity were not modified by the aging process. By comparison, phorbol ester-stimulated translocation of this activity and of PKC6 and e immunoreactivity was absent in cortex from aged animals, as well as the translocation of the calcium-dependent PKCß, also known to interact with RACK1 . These results indicate that a deficit in RACK1 may contribute to the functional impairment in PKC activation observed in aged rat brain.
FUNCTIONAL IMPAIRMENT IN PROTEIN KINASE C BY RACK1 (Receptor for Activated C Kinase 1) DEFICENCY IN AGED RAT BRAIN CORTEX
PASCALE, ALESSIA ANGELA;GOVONI, STEFANO;
1996-01-01
Abstract
Several laboratories have reported a lack of protein kinase C (PKC) activation 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 indicated that the translocation of PKC to the different subcellular compartments is controlled by protein- protein interactions . Recently, a class of proteins, termed receptors for activated C kinase (RACKS), have been described that bind PKC. The present study was conducted to determine whether alterations in RACK1, the best-characterized member of RACKS, were associated with changes in translocation and expression of PKC. Quantitative immunoblotting revealed that RACK1 content was decreased by -50% in aged rat brain cortex, compared with that in adult and middle-aged animals. The levels of calcium-independent PKC6 and E, interacting with RACK1, and related calcium-independent PKC activity were not modified by the aging process. By comparison, phorbol ester-stimulated translocation of this activity and of PKC6 and e immunoreactivity was absent in cortex from aged animals, as well as the translocation of the calcium-dependent PKCß, also known to interact with RACK1 . These results indicate that a deficit in RACK1 may contribute to the functional impairment in PKC activation observed in aged rat brain.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
