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

11 Citations (Scopus)

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

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GTP-Binding Proteins
Adenosine Diphosphate
Central Nervous System
Pertussis Toxin
Gene Expression
Proteins
Adenosine Diphosphate Ribose
Nervous System Malformations
Messenger RNA
Alloxan
Protein Subunits
Immunoblotting
Adenylyl Cyclases
Northern Blotting
Neurotransmitter Agents
Western Blotting
Pharmacology
Membranes
Antibodies

Keywords

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

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Molecular Biology

Cite this

Diabetes-induced alterations of central nervous system G proteins - ADP-ribosylation, immunoreactivity, and gene-expression studies in rat striatum. / Finco, Cristina; Abbracchio, Maria P.; Malosio, Maria Luisa; Cattabeni, Flaminio; Di Giulio, Anna M.; Paternieri, Barbara; Mantegazza, Paolo; Gorio, Alfredo.

In: Molecular and Chemical Neuropathology, Vol. 17, No. 3, 12.1992, p. 259-272.

Research output: Contribution to journalArticle

Finco, Cristina ; Abbracchio, Maria P. ; Malosio, Maria Luisa ; Cattabeni, Flaminio ; Di Giulio, Anna M. ; Paternieri, Barbara ; Mantegazza, Paolo ; Gorio, Alfredo. / Diabetes-induced alterations of central nervous system G proteins - ADP-ribosylation, immunoreactivity, and gene-expression studies in rat striatum. In: Molecular and Chemical Neuropathology. 1992 ; Vol. 17, No. 3. pp. 259-272.
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