Reduced Na+ + K+-ATPase activity in peripheral nerve of streptozotocin-diabetic rats: a role for protein kinase C?
Six weeks after induction of diabetes, the rate of ouabain-sensitive 86Rb+ accumulation, a parameter which reflects Na+ + K+-ATPase pumping activity, was significantly reduced in endoneurial preparations of sciatic nerve from untreated diabetic rats compared with that in control rats (Trial, 1, 0.19 +/- 0.09 versus 0.48 +/- 0.13 pmol/min per mg wet weight of tissue, p less than 0.001; Trial 2, 0.27 +/- 0.16 versus 0.47 +/- 0.18, p less than 0.01). This decrease in ouabain-sensitive 86Rb+ uptake was not observed in nerves from diabetic rats maintained on sorbinil (an aldose reductase inhibitor) or myo-inositol diets. Protein kinase C activity was demonstrated in the soluble fraction of a sciatic nerve homogenate by assaying for lipid-activated, Ca+-dependent phosphorylation of calf thymus histone. No significant difference in the time course of kinase C activity was observed between cytosol fractions of nerve homogenates from control and diabetic rats (control, 6.22 +/- 0.97 pmol 32P incorporated/mg cytosol protein in 50 min; diabetic, 5.32 +/- 0.71). Three low molecular weight neural proteins (each with Mr less than 29,000) were identified as substrates for protein kinase C.
Simpson
C M
CM
Department of Biochemistry, Medical School, University of Nottingham, UK.
Hawthorne
J N
JN
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D048289:Imidazolidines; D007294:Inositol / Q000378:metabolism / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D011493:Protein Kinase C / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values; D012413:Rubidium / Q000378:metabolism; D012584:Sciatic Nerve / Q000187:drug effects / Q000201:enzymology* / Q000378:metabolism; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
D001786:Blood Glucose; D007093:Imidazoles; D048289:Imidazolidines; D005632:Fructose; D007294:Inositol; D011493:Protein Kinase C; D000254:Sodium-Potassium-Exchanging ATPase; C026411:sorbinil; D005947:Glucose; D012413:Rubidium