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Neurochemical Research

, Volume 19, Issue 3, pp 321–329 | Cite as

Reduced Na+/K+ ATPase transport activity, resting membrane potential, and bradykinin-stimulated phosphatidylinositol synthesis by polyol accumulation in cultured neuroblastoma cells

  • M. A. Yorek
  • J. A. Dunlap
  • M. R. Stefani
  • E. P. Davidson
Original Articles

Abstract

In these studies we examined the effect of polyol accumulation on neural cellmyo-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 μMmyo-inositol. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose, galactose, or mannose caused a decrease inmyo- 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-stimulated32P incorporation into phosphatidylinositol compared to cells cultured in medium containing 30 mM fructose. In contrast, basal incorporation of32P into phosphatidylinositol or basal and bradykinin-stimulated32P incorporation into phosphatidylinositol 4,5-bisphosphate were not effected. Each of these cellular functions as well asmyo-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 μMmyo-inositol. The results suggest that polyol accumulation induces defects in neural cellmyo-inositol metabolism and certain cell functions which could, if they occurred in vivo, contribute to the pathological defects observed in diabetic neuropathy.

Key Words

Diabetic neuropathy myo-inositol 

polyols

sorbitol neuroblastoma cells phosphatidylinositol aldose reductase 

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Copyright information

© Plenum Publishing Corporation 1994

Authors and Affiliations

  • M. A. Yorek
    • 1
  • J. A. Dunlap
    • 1
  • M. R. Stefani
    • 1
  • E. P. Davidson
    • 1
  1. 1.Veterans Administration Medical Center, Department of Internal Medicine and Diabetes Endocrinology Research CenterUniversity of IowaIowa City

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