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Nitric oxide‐sensitive protein ADP‐ribosylation is altered in rat diabetic neuropathy
Author(s) -
Gorio Alfredo,
Donadoni M. L.,
Di Giulio A. M.
Publication year - 1995
Publication title -
journal of neuroscience research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.72
H-Index - 160
eISSN - 1097-4547
pISSN - 0360-4012
DOI - 10.1002/jnr.490400318
Subject(s) - adp ribosylation , cytosol , retina , endogeny , endocrinology , insulin , medicine , diabetes mellitus , membrane protein , biochemistry , biology , chemistry , membrane , enzyme , nad+ kinase , neuroscience
Endogenous ADP‐ribosylation of proteins was studied in retina crude extract, membrane and cytosolic fractions of control and diabetic rats. ADP‐ribosyl‐transferase activity is present in all cellular fractions, but protein ADP‐ribosylation is reduced in diabetic rat retina. At least 6 proteins are labelled in the crude extract fraction and a similar number in the membrane preparation of control animals. In these preparations from diabetic retina, only two bands were labelled, the 85 K and 36K for the crude extract, and the 97 K and 39 K for membranes. Labelling of 36 K and 39 K proteins was much less than in controls. In the cytosolic preparations of controls, two proteins of 85 K and 39 K are ADP‐ribosylated, while in diabetic rat retina cytosol, only the 85 K is labelled. Treatment of diabetic rats with insulin normalized plasma glucose levels and prevented the alterations of the extent of ADP‐ribosylation for the 38 K cytosolic, 39 K membrane and 36 K crude extracts proteins, but it failed to affect the other bands. These results suggest a hyperactivity of endogenous ADP‐ribosylases in diabetic rat retina, so that the protein sites for ADP‐ribosylation are no longer available. Since insulin treatment prevents the onset of neuropathy and of retinal G protein impairment (Abbracchio et al., J Neurosci Res 29:196–220, 1991) in diabetic rats and, in this study, normalizes ADP‐ribosylation of 39 K, 38 K and 36 K proteins, we suggest that the abnormal endogenous ADP‐ribosylation of these proteins might play a role in the onset of diabetic neuropathy. © 1995 Wiley‐Liss, Inc.