MOLECULAR NEUROSCIENCEAmelioration of retarded neurite outgrowth of dorsal root ganglion neurons by overexpression of PKCδ in diabetic ratsSakaue, Yoshio; Sanada, Mitsuru; Sasaki, Teiji; Kashiwagi, Atsunori1; Yasuda, HitoshiCAAuthor Information Division of Neurology and 1Divison of Endocrinology and Metabolism, Department of Medicine, Shiga University of Medical Science, Seta, Otsu, Shiga 520-2192 Japan CACorresponding Author: email@example.com Received 20 November 2002; accepted 8 January 2003 NeuroReport: March 3rd, 2003 - Volume 14 - Issue 3 - p 431-436 Buy SDC 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 PKCδ specific inhibitor, significantly retracted neurite outgrowth whereas Gö6976, an inhibitor specific for classical PKCs, had no effect, suggesting a significant role of PKCδ in neurite outgrowth of DRG neurons. The expression of phosphorylated PKCδ, but not total PKCδ, in DRGs was decreased in diabetic rats. When this reduced expression was restored by overexpressing the PKCδ in isolated DRG neurons, retardation of neurite outgrowth was significantly reversed in diabetic rats. These results suggest that a decrease in phosphorylated PKCδ is at least in part responsible for impaired neurite outgrowth in diabetes, and that PKCδ plays a significant role in the pathogenesis of diabetic neuropathy. This observation provides a useful clue for the treatment of diabetic neuropathy. © 2003 Lippincott Williams & Wilkins, Inc.