Glycation of brain actin in experimental diabetes.
Actin is a neuronal protein involved in axonal transport and nerve regeneration, both of which are known to be impaired in experimental diabetes. To determine if actin is subject to glycation, we rendered rats diabetic by injection of streptozotocin. Two or 6 weeks later brains were removed and a preparation of cytoskeletal proteins was analyzed by two-dimensional polyacrylamide gel electrophoresis. Brains from diabetic animals contained an extra polypeptide that migrated close to actin and reacted with monoclonal antibody C4 against actin. It was also found in a preparation of soluble synaptic proteins from diabetic rat brain, indicating that it was at least partly neuronal in origin. This polypeptide could be produced by incubation of cytoskeletal proteins from brains of nondiabetic rats with glucose-6-phosphate in vitro. The appearance of this glycated actin in diabetic animals was prevented by administration of insulin for a period of 6 weeks. We could not detect any effect of glycation in vitro on the ability of muscle G-actin to form F-actin filaments and its significance for the function of actin remains to be determined. The finding that glycation of platelet-derived actin from diabetic patients was significantly increased implies that the abnormality may also occur in clinical diabetes.
Pekiner
C
C
Department of Pharmacology and Therapeutics, University of Liverpool, England.
Cullum
N A
NA
Hughes
J N
JN
Hargreaves
A J
AJ
Mahon
J
J
Casson
I F
IF
McLean
W G
WG
D000199:Actins / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D003598:Cytoskeletal Proteins / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D015180:Electrophoresis, Gel, Two-Dimensional; D005260:Female; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate; D005958:Glucosephosphates / Q000378:metabolism; D006031:Glycosylation; D006801:Humans; D051381:Rats; D017208:Rats, Wistar
D000199:Actins; D003598:Cytoskeletal Proteins; D005958:Glucosephosphates; D019298:Glucose-6-Phosphate; D005947:Glucose