Diabetes-induced alterations of central nervous system G proteins - ADP-ribosylation, immunoreactivity, and gene-expression studies in rat striatum

Cristina Finco, Maria P. Abbracchio, Maria Luisa Malosio, Flaminio Cattabeni, Anna M. Di Giulio, Barbara Paternieri, Paolo Mantegazza, Alfredo Gorio

Research output: Contribution to journalArticle

Abstract

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 of32P-ADPribose incorporation into G protein α 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 α 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.

Original languageEnglish
Pages (from-to)259-272
Number of pages14
JournalMolecular and Chemical Neuropathology
Volume17
Issue number3
DOIs
Publication statusPublished - Dec 1992

Keywords

  • diabetic encephalopathy
  • Experimental diabetes
  • G proteins
  • rat striatum
  • transductional alterations

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Molecular Biology

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