title: Effects of protein kinase inhibitors on regeneration in vitro of adult frog sciatic sensory axons.
abstract: The effects of protein kinase inhibitors on regeneration in vitro of adult frog sciatic sensory axons were tested. Regeneration of crush-injured nerves for 8 days in serum-free medium was inhibited by staurosporine (100 nM) and H-7 (100 microM), which are both known to inhibit protein kinase C. With the use of a compartmented culture system it could be shown that H-7 exerted both local (outgrowth region) and central (ganglia) effects, the latter being more pronounced. The local effects could be due to reduction of Schwann cell proliferation by H-7. Immunohistochemistry demonstrated the presence of protein kinase C in neuronal cell bodies but not in axonal processes. Proliferation of Schwann cells was accompanied by increased protein kinase C immunoreactivity at the site of injury. H-7 caused a selective inhibition in the incorporation of radioactive phosphate into one 74 kDa protein of both ganglia and nerve but also a more general decrease in protein labelling. The results show that protein phosphorylations, possibly mediated by protein kinase C, are involved in regeneration-related mechanisms operating at both local and central levels in the adult frog sciatic sensory axons.
authors.affiliation: Department of Animal Physiology, University of Lund, Sweden.
authors.forename: P A
authors.initials: PA
authors.lastname: Ekström
authors.forename: H
authors.initials: H
authors.lastname: Bergstrand
authors.forename: A
authors.initials: A
authors.lastname: Edström
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000200:Action Potentials; D000470:Alkaloids / Q000494:pharmacology; D000818:Animals; D001369:Axons / Q000187:drug effects / Q000201:enzymology*; D002455:Cell Division; D007150:Immunohistochemistry; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D009416:Nerve Regeneration; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology*; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011896:Rana temporaria; D012583:Schwann Cells / Q000187:drug effects; D012584:Sciatic Nerve / Q000201:enzymology* / Q000502:physiology; D019311:Staurosporine
chemical_list: D000470:Alkaloids; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D019311:Staurosporine