Restoration of Na(+)-K+ pump activity and resting membrane potential by myo-inositol supplementation in neuroblastoma cells chronically exposed to glucose or galactose.
myo-Inositol uptake by culture neuroblastoma cells at a concentration of myo-inositol less than 50 microM was largely Na+ dependent. Exposing neuroblastoma cells to media supplemented with increasing concentrations of myo-inositol resulted in an increase in myo-inositol accumulation and intracellular content, but myo-inositol incorporation into phospholipids was not increased. The data indicate that myo-inositol exists as separate pools in neuroblastoma cells, and one or more of these pools may contribute to phospholipid synthesis. Exposing neuroblastoma cells to an increased concentration of glucose caused a decrease in myo-inositol uptake by two separate mechanisms. Acute exposure of the cells to 30 mM glucose caused a myo-inositol concentration-dependent decrease in Na(+)-dependent myo-inositol uptake. We propose that the acute inhibition of myo-inositol uptake by glucose is likely due to a competitive type of inhibition. Chronic exposure of cells to media containing 30 mM glucose or 30 mM galactose also caused decreases in myo-inositol uptake and incorporation into inositol phospholipids and intracellular myo-inositol content. This decrease in myo-inositol metabolism persisted at a higher concentration of external myo-inositol than the acute inhibition. Supplementing media containing 30 mM glucose or 30 mM galactose with 250 microM myo-inositol restored myo-inositol metabolism and content. The inhibition of myo-inositol uptake by cells chronically exposed to increased concentrations of glucose or galactose was due to a noncompetitive type of inhibition that was blocked by the addition of sorbinil. Chronic exposure of neuroblastoma cells to media containing 30 mM glucose or 30 mM galactose caused a decrease in Na(+)-K(+)-ATPase transport activity and resting membrane potential.(ABSTRACT TRUNCATED AT 250 WORDS)
Yorek
M A
MA
Department of Internal Medicine, Veterans Administration Medical Center, Iowa City, IA 52246.
Dunlap
J A
JA
Stefani
M R
MR
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects / Q000502:physiology; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism / Q000502:physiology; D003470:Culture Media; D004305:Dose-Response Relationship, Drug; D005690:Galactose / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007294:Inositol / Q000378:metabolism / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects* / Q000502:physiology; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism* / Q000503:physiopathology; D010743:Phospholipids / Q000378:metabolism; D011188:Potassium / Q000378:metabolism / Q000493:pharmacokinetics*; D012964:Sodium / Q000378:metabolism / Q000493:pharmacokinetics*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014407:Tumor Cells, Cultured
D003470:Culture Media; D010743:Phospholipids; D007294:Inositol; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D011188:Potassium; D005690:Galactose