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 language | English |
|---|---|
| Pages (from-to) | 259-272 |
| Number of pages | 14 |
| Journal | Molecular and Chemical Neuropathology |
| Volume | 17 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - Dec 1992 |
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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 journal › Article
}
TY - JOUR
T1 - Diabetes-induced alterations of central nervous system G proteins - ADP-ribosylation, immunoreactivity, and gene-expression studies in rat striatum
AU - Finco, Cristina
AU - Abbracchio, Maria P.
AU - Malosio, Maria Luisa
AU - Cattabeni, Flaminio
AU - Di Giulio, Anna M.
AU - Paternieri, Barbara
AU - Mantegazza, Paolo
AU - Gorio, Alfredo
PY - 1992/12
Y1 - 1992/12
N2 - 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.
AB - 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.
KW - diabetic encephalopathy
KW - Experimental diabetes
KW - G proteins
KW - rat striatum
KW - transductional alterations
UR - http://www.scopus.com/inward/record.url?scp=0027058478&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0027058478&partnerID=8YFLogxK
U2 - 10.1007/BF03160015
DO - 10.1007/BF03160015
M3 - Article
C2 - 1492884
AN - SCOPUS:0027058478
VL - 17
SP - 259
EP - 272
JO - Journal of Molecular Neuroscience
JF - Journal of Molecular Neuroscience
SN - 0895-8696
IS - 3
ER -