Diminished specific activity of cytosolic protein kinase C in sciatic nerve of streptozocin-induced diabetic rats and its correction by dietary myo-inositol.
The impaired Na(+)-K(+)-ATPase activity in peripheral nerve from diabetic rats is prevented by dietary myo-inositol (MI) supplementation in vivo and corrected by protein kinase C (PKC) agonists in vitro, suggesting that PKC may mediate the effects of nerve MI depletion on Na(+)-K(+)-ATPase activity. However, little is known about the effect of diabetes on PKC activity or peptide in rat peripheral nerve. Therefore, the effect of streptozocin-induced diabetes and dietary MI supplementation on the activity and distribution of PKC in rat sciatic nerve homogenates and cytosolic and particulate fractions was explored with histone phosphorylation assay and Western-blot analysis. PKC activity but not peptide was selectively decreased in the cytosolic fraction by streptozocin-induced diabetes, and this abnormality was partially corrected by dietary MI supplementation. These results suggest that altered MI metabolism may affect nerve PKC specific activity, and this alteration may play a role in reduced Na(+)-K(+)-ATPase activity and blunted regenerative response in diabetic nerve.
Kim
J
J
Department of Biological Chemistry, University of Pittsburgh, Pennsylvania.
Rushovich
E H
EH
Thomas
T P
TP
Ueda
T
T
Agranoff
B W
BW
Greene
D A
DA
D000284:Administration, Oral; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D001835:Body Weight / Q000187:drug effects; D003600:Cytosol / Q000201:enzymology*; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D004032:Diet; D004075:Diglycerides / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D007294:Inositol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*; D008297:Male; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism* / Q000493:pharmacokinetics; D051381:Rats; D011919:Rats, Inbred Strains; D012584:Sciatic Nerve / Q000201:enzymology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D013311:Streptozocin
D001786:Blood Glucose; D004075:Diglycerides; D006657:Histones; D007294:Inositol; D013311:Streptozocin; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase