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Decreased alpha-endosulfine, an endogenous regulator of ATP-sensitive potassium channels, in brains from adult Down syndrome patients

  • S. H. Kim
  • G. Lubec
Chapter

Summary

Alpha-endosulfine has the ability to block ATP-sensitive potassium (KATP) channels and stimulate insulin release in ß cells like sulfonylurea. Alpha-endosulfine is expressed in a wide range of tissue, including brain and endocrine tissues. Although KATP channels are also present in brain and its regulators have been reported to be involved in the release of neurotransmitters such as acetylcholine that plays an important role in cognitive function, the neurobiological role of α-endosulfine has not been studied yet. We examined the expression levels of α-endosulfine protein in frontal cortex and cerebellum from patients with Down syndrome (DS) showing Alzheimer’s disease (AD) pathology using Western blotting. In frontal cortex, α-endosulfine was detected in all of 10 controls, but only 1 (from female) out of 8 DS with weak density. In cerebellum, α-endosulfine was also detected in all of 9 controls, but only 1 (from male) out of 6 DS with weak density. The considerably decreased α-endosulfine could result in the continuous opening of KATP channels and the subsequent decrease of neurotransmitters release associated with cognition. This study is of significance providing evidence for a biological role of α-endosulfine in brain and α-endosulfine protein could be a pharmacological target for therapeutic intervention.

Keywords

Frontal Cortex Down Syndrome KATP Channel Impaired Glucose Metabolism Weak Density 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. Aguilar-Bryan L, Nichols CG, Wechsler SW, Clement JP4th, Boyd AE3rd, Gonzalez G,Herrera-Sosa H, Nguy K, Bryan J, Nelson DA (1995) Cloning of the beta cell highaffinity sulfonylurea receptor: a regulator of insulin secretion. Science 268: 423–426PubMedCrossRefGoogle Scholar
  2. Amoroso S, Schmid-Antomarchi H, Fosset M, Lazdunski M (1990) Glucose, antidiabetic sulfonylureas and neurotransmitter release. Role of ATP-sensitive K+ channels.Science 247: 852–854PubMedCrossRefGoogle Scholar
  3. Clement JP4th, Kunjilwar K, Gonzalez G, Schwantstecher M, Panten U, Aguilar-Bryan L,Bryan J (1997) Association and stoichiometry of K(ATP) channel subunits. Neuron 18: 827–838PubMedCrossRefGoogle Scholar
  4. Crepel V, Rovira C, Ben-Ari Y (1993) The K+ channel opener diazoxide enhances glutamatergic currents and reduces GABAergic currents in hippocampal neurons.J Neurophysiol 69: 494–503PubMedGoogle Scholar
  5. During MJ, Leone P, Davis KE, Kerr D, Sherwin RS (1995) Glucose modulates rat substantia nigra GABA release in vivo via ATP-ensitive potassium channels. J Clin Invest 95: 2403–2408PubMedCrossRefGoogle Scholar
  6. Edwards G, Weston AH (1993) The pharmacology of ATP-sensitive potassium channels.Ann Rev Pharmacol Toxicol 33: 597–637CrossRefGoogle Scholar
  7. Fiedler JL, Epstein CJ, Rapoport SI, Caviedes R, Caviedes P (1994) Regional alteration of cholingeric function in central neurons of trisomy 16 mouse fetuses, an animal model of human trisomy 21 (Down syndrome). Brain Res 658: 27–32PubMedCrossRefGoogle Scholar
  8. Godridge H, Reynolds GP, Czudek C, Calcutt NA, Benton M (1987) Alzheimer-like neurotransmitter deficits in adult Down’s syndrome brain tissue. J Neurol Neurosurg Psychiatry 50: 775–778PubMedCrossRefGoogle Scholar
  9. Gold PE (1995) Role of glucose in regulating the brain and cognition. Am J Clin Nutr[Suppl] 61: 987S–995SPubMedGoogle Scholar
  10. Grenhoff J, Johnson SW (1996) Sulfonylureas enhance GABAA synaptic potentials in rat midbrain dopamine neurons. Acta Physiol Scand 156: 147–148PubMedCrossRefGoogle Scholar
  11. Haj-Dahmans S, Laporte AM, Vantalon V, Fattaccini CM, Hamon M, Lanfumey L (1993) Possible involvement of K(ATP) channels in the control of 5-HT neurons.Brain Res 614: 270–278CrossRefGoogle Scholar
  12. Heron L, Virsolvy A, Peyrollier K, Gribble F, Le Cam A, Ashcroft FM, Bataille D (1998) Human a-endosulfine, a possible regulator of sulfonylurea-sensitive KATP channel:molecular cloning, expression and biological properties. Proc Natl Acad Sci USA 95: 8387–8391PubMedCrossRefGoogle Scholar
  13. Heron L, Virsolvy A, Apiou F, Le Cam A, Bataille D (1999) Isolation, characterization,and chromosomal localization of the human ENSA gene that encodes alpha-endosulfine, a regulator of beta-cell K(ATP) channels. Diabetes 48: 1873–1876PubMedCrossRefGoogle Scholar
  14. Inagaki N, Gonoi T, Clement JP4th, Namba N, Inazawa J, Gonzalez G, Aguilar-Bryan L,Seino S, Bryan J (1995) Reconstitution of IKATP: an inward rectifier subunit plus sulfonylurea receptor. Science 270: 1166–1170PubMedCrossRefGoogle Scholar
  15. Kish SJ, Distefano LM, Dozic S, Robitaille Y, Rajput A, Deck JH, Hornykiewicz O (1990) [3H] Vesamicol binding in human brain cholinergic deficiency disorders.Neurosci Lett 117: 347–352PubMedCrossRefGoogle Scholar
  16. Korol DL, Gold PE (1998) Glucose, memory, and aging. Am J Clin Nutr [Suppl] 67:764S–771SPubMedGoogle Scholar
  17. Kozlowski RZ, Hales CN, Ashford MLJ (1989) Dual effects of diazoxide on ATP-K currents recorded from an insulin-secreting cell line. Br J Pharmacol 97: 1039–1050PubMedCrossRefGoogle Scholar
  18. Labudova O, Cairns N, Kitzmuller E, Lubec G (1999) Impaired brain glucose metabolism in patients with Down syndrome. J Neural Transm [Suppl] 57: 247–256Google Scholar
  19. Lazdunski M (1996) Ion channel effects of antidiabetic sulfonylureas. Horm Metab Res 28: 488–495PubMedCrossRefGoogle Scholar
  20. Lauritzen I, De Weille JR, Lazdunski M (1997) The potassium channel opener (-)-cromakalim prevents glutamate-induced cell death in hippocampal neurons. J Neurochem 69: 1570–1579PubMedCrossRefGoogle Scholar
  21. Lee K, Brownhill V, Richardson PJ (1997) Antidiabetic sulphonylureas stimulate acetylcholine release from striatal cholinergic interneruons through inhibition of K(ATP) channel activity. J Neurochem 69: 1774–1776PubMedCrossRefGoogle Scholar
  22. Lopez L, Sannita WG (1997) Glucose availability and the electrophysiology of the human visual system. Clin Neurosci 4: 336–340PubMedGoogle Scholar
  23. Mann DM, Yates PO, Marcyniuk B, Ravindra CR (1985) Pathological evidence for neurotransmitter deficits in Down’s syndrome of middle age. J Ment Defic Res 29: 125–135PubMedGoogle Scholar
  24. Miller RJ (1990) Glucose-regulated potassium channels are sweet news for neurobiologists. Trends Neurosci 13: 197–199PubMedCrossRefGoogle Scholar
  25. Mourre C, Widmann C, Lazdunski M (1990) Sulfonylurea binding sites associated with ATP-regulated K+ channels in the central nervous system: autoradiographic analysis of their distribution and ontogenesis, and of their localization in mutant mice cerebellum. Brain Res 519: 29–43PubMedCrossRefGoogle Scholar
  26. Mourre C, Widmann C, Lazdunski M (1991) Specific hippocampal lesions indicate the presence of sulfonylurea binding sites associated to ATP-sensitive K+ channels both post-synpatically and on mossy fibers. Brain Res 540: 340–344PubMedCrossRefGoogle Scholar
  27. Peyrollier K, Heron L, Virsolvy-Vergine A, Le Cam A, Bataille D (1996) Alpha endosulfine is a novel molecule, structurally related to a family of phosphoproteins. Biochem Biophys Res Commun 223: 583–586PubMedCrossRefGoogle Scholar
  28. Quast U (1992) Potassium channel openers: pharmacological and clinical aspects. Fundam Clin Pharmacol 6: 279–293PubMedCrossRefGoogle Scholar
  29. Reynolds GP, Godridge H (1985) Alzheimer-like brain monoamie deficits in adults with Down’s syndrome. Lancet ii: 1368–1369CrossRefGoogle Scholar
  30. Reynolds GP, Warner CE (1988) Amino acid neurotransmitter deficits in adult Down’s syndrome brain tissue. Neurosci Lett 94: 224–227PubMedCrossRefGoogle Scholar
  31. Sakuta H (1995) ATP-sensitive potassium channel and hormone/neuropeptide. Nippon Naibunpi Gakkai Zasshi 71: 579–586PubMedGoogle Scholar
  32. Sakura H, Ammala C, Smith PA, Gribble FM, Ashcroft FM (1995) Cloning and functional expression of the cDNA encoding a novel ATP-sensitive potassium channels subunit expressed in pancreatic beta-cells, brain, heart and skeletal muscle. FEBS Lett 377: 338–344PubMedCrossRefGoogle Scholar
  33. Schapiro MB, Haxby JV, Grady CL (1992) Nature of mental retardation and dementia in Down syndrome: study with PET, CT, and neuropsychology. Neurobiol Aging 13: 723–734PubMedCrossRefGoogle Scholar
  34. Schmid-Antomarchi H, De Weille JR, Fosset M, Lazdunski M (1987) The receptor for antidiabetic sulfonylureas controls the activity of the ATP-modulated K+ channel in insulin-secreting cells. J Biol Chem 262: 15840–15844PubMedGoogle Scholar
  35. Schwappach B, Zerangue N, Jan YN, Jan LY (2000) Molecular basis for K(ATP) assembly: transmembrane interactions mediate association of a K+ channel with an ABC transporter. Neuron 26: 155–167PubMedCrossRefGoogle Scholar
  36. Shyng S, Nichols CG (1997) Octameric stoichiometry of the KATP channel complex. J Gen Physiol 110: 655–664PubMedCrossRefGoogle Scholar
  37. Sturgess NC, Hales CN, Cook DL, Ashford MLJ (1985) The sulphonylurea receptor may be an ATP-sensitive K+ channel. Lancet ii: 474–475CrossRefGoogle Scholar
  38. Tucker SJ, Gribble FM, Zhao C, Trapp S, Ashcroft FM (1997) Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulfonylurea receptor. Nature 387: 179–183PubMedCrossRefGoogle Scholar
  39. Virsolvy-Vergine A, Leray H, Kuroki S, Lupo B, Dufour M, Bataille D (1992) Endosulfine, an endogenous peptidic ligand for the sulfonylurea receptor: purification and partial characterization from ovine brain. Proc Natl Acad Sci USA 89: 6629– 6633PubMedCrossRefGoogle Scholar
  40. Virsolvy-Vergine A, Salazar G, Sillard R, Denoroy L, Mutt V, Bataille D (1996) Endosulfine, endogenous ligand for the sulfonylurea receptor: isolation from porcine brain and partial structural determination of the alpha form. Diabetologia 39: 135–141PubMedCrossRefGoogle Scholar
  41. Yates CM, Simpson J, Gordon A, Maloney AF, Allison Y, Ritchie IM, Urquhart A (1983) Catecholamines and cholinergic enzymes in pre-senile and senile Alzheimer-type dementia and Down’s syndrome. Brain Res 280: 119–126PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag/Wien 2001

Authors and Affiliations

  • S. H. Kim
    • 1
  • G. Lubec
    • 1
  1. 1.Department of PediatricsUniversity of ViennaViennaAustria

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