Protein kinase C isozyme expression in sciatic nerves and spinal cords of experimentally diabetic rats.
Changes in the expression and activation of protein kinase C (PKC) have been implicated in the pathogenesis of diabetic neuropathy. Recent studies in liver, retina, and cardiovascular tissues from experimentally diabetic rats have demonstrated that diabetes has a selective effect on the expression and subcellular distribution of isozymes of PKC. In the light of this evidence, we investigated the expression of the PKC isozymes alpha, betaI, betaII, and gamma in sciatic nerves, spinal cords, and in the L4,5 dorsal root ganglia from streptozotocin-induced diabetic rats. Six weeks of diabetes had differential effects on the expression and distribution of PKC isozymes in sciatic nerves and spinal cords. In the sciatic nerves there was an apparent translocation of the alpha isoform from the cytosolic to the particulate fractions, the betaII isoform was reduced in the cytosolic fraction, and the betaI and gamma isoforms were unaffected. The changes in the isozyme immunoreactivities in the nerves were not a direct result of changes in either spinal cord or dorsal root ganglia alone, suggesting that diabetes has different effects on motor and sensory fibres and/or on Schwann cells. In nerves that had been crushed 14 days previously there was an increase in total PKC alpha immunoreactivity. This increase was potentiated in diabetic rats. On the other hand, PKC betaII immunoreactivity in crushed nerves was unaffected by diabetes. The data are consistent with diabetes-induced changes in expression of PKC betaII contributing to nerve damage, and changes in PKC alpha being a consequence of it.
Roberts
R E
RE
Department of Pharmacology and Therapeutics, University of Liverpool, UK. MQZRER@mqn1.phpharm.nott.ac.uk
McLean
W G
WG
D000818:Animals; D003600:Cytosol / Q000201:enzymology; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology*; D005260:Female; D005727:Ganglia, Spinal / Q000201:enzymology; D007527:Isoenzymes / Q000096:biosynthesis*; D009046:Motor Neurons / Q000201:enzymology; D009412:Nerve Fibers / Q000201:enzymology; D009475:Neurons, Afferent / Q000201:enzymology; D016133:Polymerase Chain Reaction; D011493:Protein Kinase C / Q000096:biosynthesis*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012584:Sciatic Nerve / Q000201:enzymology*; D013116:Spinal Cord / Q000201:enzymology*; D013997:Time Factors; D014158:Transcription, Genetic
D007527:Isoenzymes; D012333:RNA, Messenger; C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha