title: Polyol pathway and protein kinase C activity of rat Schwannoma cells.
abstract: BACKGROUND
  Polyol pathway hyperactivity-induced decreases in protein kinase C (PKC) activities have been proposed as a pathogenic mechanism of diabetic neuropathy. Increased PKC activities have recently been invoked in the pathogenesis of other diabetic complications, especially retinopathy, nephropathy, and macroangiopathy. However, it remains unclear whether PKC activities in neural cells such as Schwann cells are increased, decreased, or unchanged. This study investigated the effects of high glucose and increased polyol pathway activity on neural cell growth and PKC activities.
  
  
  METHODS
  Rat Schwannoma cells were cultured in 5.5 or 20 mM glucose in the presence or absence of an aldose reductase inhibitor, epalrestat (1 microM) for 14 days. Proliferation activities, PKC activities, and the protein expression of PKC isoforms were measured.
  
  
  RESULTS
  Proliferation and PKC activities under the 20 mM glucose condition were significantly decreased compared to those under the 5.5 mM glucose condition and were prevented by epalrestat. Among PKC isoforms, the protein expression of PKC-alpha under the 20 mM glucose condition was significantly reduced compared to that under the 5.5 mM glucose condition. Epalrestat significantly inhibited the decreased expression of PKC-alpha protein. There were no significant changes in the protein expression of PKC-beta.
  
  
  CONCLUSIONS
  These results suggest that PKC, especially PKC-alpha activity, is decreased in Schwann cells exposed to high glucose and that this deficit is mediated through polyol pathway hyperactivity.
authors.affiliation: The Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya, Japan.
authors.forename: Hideki
authors.initials: H
authors.lastname: Kamiya
authors.forename: Jiro
authors.initials: J
authors.lastname: Nakamura
authors.forename: Yoji
authors.initials: Y
authors.lastname: Hamada
authors.forename: Eitaro
authors.initials: E
authors.lastname: Nakashima
authors.forename: Keiko
authors.initials: K
authors.lastname: Naruse
authors.forename: Koichi
authors.initials: K
authors.lastname: Kato
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Yasuda
authors.forename: Nigishi
authors.initials: N
authors.lastname: Hotta
mesh_terms: D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D003929:Diabetic Neuropathies / Q000201:enzymology*; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005632:Fructose / Q000378:metabolism; D005947:Glucose / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D009442:Neurilemmoma; D011108:Polymers / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051381:Rats; D012236:Rhodanine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013012:Sorbitol / Q000378:metabolism; D053778:Thiazolidines; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000201:enzymology / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011108:Polymers; D053778:Thiazolidines; C024617:polyol; D005632:Fructose; C038131:epalrestat; D007294:Inositol; D013012:Sorbitol; D012236:Rhodanine; D000449:Aldehyde Reductase; C497260:Prkcd protein, rat; C087857:protein kinase C gamma; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D005947:Glucose