Nitric oxide-sensitive protein ADP-ribosylation is altered in rat diabetic neuropathy.
Endogenous ADP-ribosylation of proteins was studied in retina crude extract, membrane and cytosolic fractions of control and diabetic rats. ADP-ribosyltransferase 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 36 K 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.
Gorio
A
A
Department of Medical Pharmacology, University of Milano, Italy.
Donadoni
M L
ML
Di Giulio
A M
AM
D000244:Adenosine Diphosphate / Q000378:metabolism*; D000818:Animals; D001345:Autoradiography; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D004586:Electrophoresis; D019204:GTP-Binding Proteins; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012160:Retina
D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D019204:GTP-Binding Proteins