title: Amelioration of retarded neurite outgrowth of dorsal root ganglion neurons by overexpression of PKCdelta in diabetic rats.
abstract: To examine which isoform of protein kinase C (PKC) may be associated with impaired nerve regeneration in diabetes, we compared neurite outgrowth of isolated dorsal root ganglion (DRG) neurons in streptozocin (STZ)-induced diabetic and control rats. Neurite outgrowth was significantly retarded in diabetic neurons. Rottlerin, a PKCdelta specific inhibitor, significantly retracted neurite outgrowth whereas Gö6976, an inhibitor specific for classical PKCs, had no effect, suggesting a significant role of PKCdelta in neurite outgrowth of DRG neurons. The expression of phosphorylated PKCdelta, but not total PKCdelta, in DRGs was decreased in diabetic rats. When this reduced expression was restored by overexpressing the PKCdelta in isolated DRG neurons, retardation of neurite outgrowth was significantly reversed in diabetic rats. These results suggest that a decrease in phosphorylated PKCdelta is at least in part responsible for impaired neurite outgrowth in diabetes, and that PKCdelta plays a significant role in the pathogenesis of diabetic neuropathy. This observation provides a useful clue for the treatment of diabetic neuropathy.
authors.affiliation: Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Sakaue
authors.forename: Mitsuru
authors.initials: M
authors.lastname: Sanada
authors.forename: Teiji
authors.initials: T
authors.lastname: Sasaki
authors.forename: Atsunori
authors.initials: A
authors.lastname: Kashiwagi
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Yasuda
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000503:physiopathology*; D003929:Diabetic Neuropathies / Q000503:physiopathology*; D005727:Ganglia, Spinal / Q000503:physiopathology*; D006801:Humans; D016501:Neurites / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism* / Q000494:pharmacology; D051745:Protein Kinase C-delta; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: C497260:Prkcd protein, rat; C497258:PRKCD protein, human; D011493:Protein Kinase C; D051745:Protein Kinase C-delta