title: Reduced Na+/K+ ATPase transport activity, resting membrane potential, and bradykinin-stimulated phosphatidylinositol synthesis by polyol accumulation in cultured neuroblastoma cells.
abstract: In these studies we examined the effect of polyol accumulation on neural cell myo-inositol metabolism and properties. Neuroblastoma cells were cultured for two weeks in media containing 30 mM glucose, fructose, galactose or mannose with or without 0.4 mM sorbinil or 250 microM myo-inositol. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose, galactose, or mannose caused a decrease in myo- inositol content and myo-[2-3H]inositol accumulation and incorporation into phosphoinositides compared to cells cultured in unsupplemented medium or medium containing 30 mM fructose as an osmotic control. These monosaccharides each caused an increase in intracellular polyol levels with galactitol > sorbitol = mannitol accumulation. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose, galactose, or mannose caused a significant decrease in Na+/K+ ATPase transport activity, resting membrane potential, and bradykinin-stimulated 32P incorporation into phosphatidylinositol compared to cells cultured in medium containing 30 mM fructose. In contrast, basal incorporation of 32P into phosphatidylinositol or basal and bradykinin-stimulated 32P incorporation into phosphatidylinositol 4,5-bisphosphate were not effected. Each of these cellular functions as well as myo-inositol metabolism and content and polyol levels remained near control values when 0.4 mM sorbinil, an aldose reductase inhibitor, was added to the glucose, galactose, or mannose supplemented media. myo-Inositol metabolism and content and bradykinin-stimulated phosphatidylinositol synthesis were also maintained when media containing 30 mM glucose, galactose, or mannose was supplemented with 250 microM myo-inositol. The results suggest that polyol accumulation induces defects in neural cell myo-inositol metabolism and certain cell functions which could, if they occurred in vivo, contribute to the pathological defects observed in diabetic neuropathy.
authors.affiliation: Veterans Administration Medical Center, Iowa City, Iowa 52246.
authors.forename: M A
authors.initials: MA
authors.lastname: Yorek
authors.forename: J A
authors.initials: JA
authors.lastname: Dunlap
authors.forename: M R
authors.initials: MR
authors.lastname: Stefani
authors.forename: E P
authors.initials: EP
authors.lastname: Davidson
mesh_terms: D000818:Animals; D001920:Bradykinin / Q000494:pharmacology*; D002460:Cell Line; D005632:Fructose / Q000378:metabolism / Q000494:pharmacology; D005690:Galactose / Q000378:metabolism / Q000494:pharmacology; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology; D007294:Inositol / Q000378:metabolism; D007700:Kinetics; D008358:Mannose / Q000378:metabolism / Q000494:pharmacology; D008564:Membrane Potentials / Q000502:physiology*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism*; D010716:Phosphatidylinositols / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013012:Sorbitol / Q000378:metabolism; D013402:Sugar Alcohols / Q000378:metabolism*; D014407:Tumor Cells, Cultured
chemical_list: D010716:Phosphatidylinositols; D013402:Sugar Alcohols; D005632:Fructose; D007294:Inositol; D013012:Sorbitol; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D008358:Mannose; D001920:Bradykinin; D005690:Galactose