Altered vitamin E status in Niemann-Pick type C disease

L. Ulatowski, R. Parker, C. Davidson, N. Yanjanin, T. J. Kelley, D. Corey, J. Atkinson, F. Porter, H. Arai, Steven U. Walkley, D. Manor

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Vitamin E (alpha-tocopherol) is the major lipid-soluble antioxidant in many species. Niemann-Pick type C (NPC) disease is a lysosomal storage disorder caused by mutations in the NPC1 or NPC2 gene, which regulates lipid transport through the endocytic pathway. NPC disease is characterized by massive intracellular accumulation of unesterified cholesterol and other lipids in lysosomal vesicles. We examined the roles that NPC1/2 proteins play in the intracellular trafficking of tocopherol. Reduction of NPC1 or NPC2 expression or function in cultured cells caused a marked lysosomal accumulation of vitamin E in cultured cells. In vivo, tocopherol significantly accumulated in murine Npc1-null and Npc2-null livers, Npc2-null cerebella, and Npc1-null cerebral cortices. Plasma tocopherol levels were within the normal range in Npc1-null and Npc2-null mice, and in plasma samples from human NPC patients. The binding affinity of tocopherol to the purified sterol-binding domain of NPC1 and to purified NPC2 was significantly weaker than that of cholesterol (measurements kindly performed by R. Infante, University of Texas Southwestern Medical Center, Dallas, TX). Taken together, our observations indicate that functionality of NPC1/2 proteins is necessary for proper bioavailability of vitamin E and that the NPC pathology might involve tissue-specific perturbations of vitamin E status.

Original languageEnglish (US)
Pages (from-to)1400-1410
Number of pages11
JournalJournal of Lipid Research
Volume52
Issue number7
DOIs
StatePublished - Jul 2011

Fingerprint

Type C Niemann-Pick Disease
Tocopherols
Vitamin E
Lipids
Cultured Cells
Cholesterol
Cells
Plasmas
alpha-Tocopherol
Pathology
Sterols
Liver
Cerebral Cortex
Cerebellum
Biological Availability
Reference Values
Proteins
Antioxidants
Genes
Tissue

Keywords

  • Niemann-Pick disease
  • Nutrition
  • Oxidized lipids

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology
  • Endocrinology

Cite this

Ulatowski, L., Parker, R., Davidson, C., Yanjanin, N., Kelley, T. J., Corey, D., ... Manor, D. (2011). Altered vitamin E status in Niemann-Pick type C disease. Journal of Lipid Research, 52(7), 1400-1410. https://doi.org/10.1194/jlr.M015560

Altered vitamin E status in Niemann-Pick type C disease. / Ulatowski, L.; Parker, R.; Davidson, C.; Yanjanin, N.; Kelley, T. J.; Corey, D.; Atkinson, J.; Porter, F.; Arai, H.; Walkley, Steven U.; Manor, D.

In: Journal of Lipid Research, Vol. 52, No. 7, 07.2011, p. 1400-1410.

Research output: Contribution to journalArticle

Ulatowski, L, Parker, R, Davidson, C, Yanjanin, N, Kelley, TJ, Corey, D, Atkinson, J, Porter, F, Arai, H, Walkley, SU & Manor, D 2011, 'Altered vitamin E status in Niemann-Pick type C disease', Journal of Lipid Research, vol. 52, no. 7, pp. 1400-1410. https://doi.org/10.1194/jlr.M015560
Ulatowski L, Parker R, Davidson C, Yanjanin N, Kelley TJ, Corey D et al. Altered vitamin E status in Niemann-Pick type C disease. Journal of Lipid Research. 2011 Jul;52(7):1400-1410. https://doi.org/10.1194/jlr.M015560
Ulatowski, L. ; Parker, R. ; Davidson, C. ; Yanjanin, N. ; Kelley, T. J. ; Corey, D. ; Atkinson, J. ; Porter, F. ; Arai, H. ; Walkley, Steven U. ; Manor, D. / Altered vitamin E status in Niemann-Pick type C disease. In: Journal of Lipid Research. 2011 ; Vol. 52, No. 7. pp. 1400-1410.
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