The post-translational arginylation of proteins in different regions of the rat brain

HALLAK, MARTA E; BONGIOVANNI, GUILLERMINA; BARRA, HÉCTOR S.

Springfield, Illinois, U.S.A..

Simposio; Second International Springfield Symposium of advances in Alzheimer Therapy; 1991

Southern Illinois univ. school medicine, dep. pharmacology and psychiatry, Springfield IL

The posttranslational incorporation of arginine into proteins catalyzed by arginyl-tRNA protein transferase was determined in vitro in different rat brain regions. The incorporation was found in all the regions studied, although with different specific activities (pmol [14C]arginine incorporated/mg protein). Of the regions studied, hippocampus had the highest specific activity followed by striatum, medulla oblongata, cerebellum, and cerebral cortex. Electrophoretic analysis of the [14C]arginyl proteins from the different regions followed by autoradiography and scanner densitometry showed at least 13 polypeptide bands that were labeled with [14C]arginine. The radioactive bands were qualitatively coincident with protein bands revealed by Coomassie Blue. There were peaks that showed different proportions of labeling in comparison with peaks of similar molecular mass from total brain. Most notable because of their high proportions were those of molecular mass 125 kDa in hippocampus, striatum, and cerebral cortex; 112 and 98 kDa in striatum and cerebellum; and 33 kDa in hippocampus and striatum. In lower proportions than in total brain were the peaks of 33 kDa in medulla oblongata and cerebral cortex and of 125 kDa in medulla oblongata. For many proteins the addition of arginine by arginyl-tRNA to the N-terminus is required for their degradation by the ubiquitin pathway (Fegber and Ciechanover, 1987, Nature 326). Since there is ubiquitination of neuronal inclusions in Alzheimer´s desease, ubiquitin accumulation may be related to the process of neurodegeneration (Manetto et al., 1988, PNAS 85).