Previous studies from our laboratory have suggested that diabetes-associated central nervous system abnormalities are characterized by progressive alterations of neurotransmitters and of transductional Gi/Go proteins. In this study, we have further characterized these abnormalities in the striatum of alloxan-diabetic rats by means of adenosine 5'-diphosphate (ADP)-ribosylation, and Western and Northern blotting techniques. Fourteen weeks after diabetes induction, pertussis-toxin (PTX) catalyzed ADP-ribosylation of Gi/Go proteins was markedly reduced in diabetic animals, as shown by a clear decrease of P-32-ADPribose incorporation into G protein alpha subunits. In agreement with our previous pharmacological studies that showed a reduction of Gi-mediated modulation of adenylate cyclase activity only at this stage of diabetes, no changes in PTX-mediated ADP-ribosylation were observed earlier (5-wk diabetes). Immunoblotting studies performed by using antibodies selectively raised against Gi-2, Go, and Gs proteins did not reveal any differences between control and diabetic animals at any stage of diabetes. Similarly, the mRNAs corresponding to the alpha subunits of Gi-2, Go, and Gs proteins did not show any marked changes in chronic diabetic rats with respect to control animals. It is therefore concluded that diabetes is associated with development of a time-related alteration of cerebral Gi/Go proteins and that this defect is not owing to gross changes in either content of G proteins or mRNA level, but probably reflects modifications of G protein's structure or physiological status affecting the coupling with membrane effector systems and the sensitivity to PTX.
DIABETES-INDUCED ALTERATIONS OF CENTRAL-NERVOUS-SYSTEM G-PROTEINS - ADP-RIBOSYLATION, IMMUNOREACTIVITY, AND GENE-EXPRESSION STUDIES IN RAT STRIATUM / C. FINCO, M. ABBRACCHIO, M. MALOSIO, F. CATTABENI, A. DIGIULIO, B. PATERNIERI, P. MANTEGAZZA, A. GORIO. - In: MOLECULAR AND CHEMICAL NEUROPATHOLOGY. - ISSN 1044-7393. - 17:3(1992), pp. 259-272.
|Titolo:||DIABETES-INDUCED ALTERATIONS OF CENTRAL-NERVOUS-SYSTEM G-PROTEINS - ADP-RIBOSYLATION, IMMUNOREACTIVITY, AND GENE-EXPRESSION STUDIES IN RAT STRIATUM|
ABBRACCHIO, MARIA PIA (Secondo)
GORIO, ALFREDO (Ultimo)
|Parole Chiave:||diabetic encephalopathy; Experimental diabetes; G proteins; rat striatum; transductional alterations|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||1992|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1007/BF03160015|
|Appare nelle tipologie:||01 - Articolo su periodico|