Isoform specific reductions in Na+,K(+)-ATPase catalytic (alpha) subunits in the nerve of rats with streptozotocin-induced diabetes.
Na+,K(+)-ATPase activity in nerve is reduced in rats with streptozotocin-induced diabetes; three different isoforms of the alpha (catalytic) subunit of the enzyme are present in nerve. Using western blot to determine subunit isoform polypeptide levels in sciatic nerve, we found a substantial reduction in alpha 1-isoform polypeptide (88% at 3 weeks, 94% at 8 weeks) after induction of diabetes by streptozotocin. Reductions in alpha 2 and alpha 3 polypeptide were smaller and not statistically significant. The reduction in amount of all three isoform polypeptides in the nerve of 3-week diabetic animals was corrected by administration of insulin. Accumulation of alpha 1 polypeptide at a nerve ligature indicated that rapid transport of that polypeptide in nerve occurs with normal kinetics. The results implicate a specific marked deficit in alpha 1, much more than alpha 2 or alpha 3, catalytic subunit isoform of Na+,K(+)-ATPase in the pathogenesis of diabetic neuropathy.
Fink
D J
DJ
Department of Neurology, University of Michigan, Ann Arbor 48105.
Datta
S
S
Mata
M
M
D000818:Animals; D015153:Blotting, Western; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007536:Isomerism; D008297:Male; D009474:Neurons / Q000737:chemistry* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000032:analysis* / Q000378:metabolism; D013311:Streptozocin
D013311:Streptozocin; D000254:Sodium-Potassium-Exchanging ATPase