Next Article in Journal
Dietary Intervention Restored Menses in Female Athletes with Exercise-Associated Menstrual Dysfunction with Limited Impact on Bone and Muscle Health
Next Article in Special Issue
Vitamin E Supplementation in Chemical Colorectal Carcinogenesis: A Two-Edged Knife
Previous Article in Journal
Association between Intake of Sugar-Sweetened Beverages and Circulating 25-Hydroxyvitamin D Concentration among Premenopausal Women
Previous Article in Special Issue
The Effects of α-Tocopherol on Bone: A Double-Edged Sword?
Article Menu

Export Article

Open AccessArticle
Nutrients 2014, 6(8), 3000-3017; doi:10.3390/nu6083000

Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice

1
Departamento de Gastroenterología, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago 8330024, Chile
2
Departamento de Biología Celular y Molecular, Facultad de Ciencias Biológicas, Pontificia Universidad Católica de Chile, Santiago 8330025, Chile
3
Laboratory of Molecular Physiology and Channelopaties, Department of Experimental and Health Sciences, Universitat Pompeu Fabra, Barcelona 08003, Spain
4
Center FONDAP for Genome Regulation, Santiago 8370415, Chile
*
Authors to whom correspondence should be addressed.
Received: 10 March 2014 / Revised: 16 July 2014 / Accepted: 18 July 2014 / Published: 30 July 2014
(This article belongs to the Special Issue Vitamin E Nutrition and Metabolism)
View Full-Text   |   Download PDF [2300 KB, uploaded 30 July 2014]   |  

Abstract

Niemann-Pick C (NPC) disease is a fatal neurodegenerative disorder characterized by the accumulation of free cholesterol in lysosomes. We have previously reported that oxidative stress is the main upstream stimulus activating the proapoptotic c-Abl/p73 pathway in NPC neurons. We have also observed accumulation of vitamin E in NPC lysosomes, which could lead to a potential decrease of its bioavailability. Our aim was to determine if dietary vitamin E supplementation could improve NPC disease in mice. NPC mice received an alpha-tocopherol (α-TOH) supplemented diet and neurological symptoms, survival, Purkinje cell loss, α-TOH and nitrotyrosine levels, astrogliosis, and the c-Abl/p73 pathway functions were evaluated. In addition, the effect of α-TOH on the c-Abl/p73 pathway was evaluated in an in vitro NPC neuron model. The α-TOH rich diet delayed loss of weight, improved coordination and locomotor function and increased the survival of NPC mice. We found increased Purkinje neurons and α-TOH levels and reduced astrogliosis, nitrotyrosine and phosphorylated p73 in cerebellum. A decrease of c-Abl/p73 activation was also observed in the in vitro NPC neurons treated with α-TOH. In conclusion, our results show that vitamin E can delay neurodegeneration in NPC mice and suggest that its supplementation in the diet could be useful for the treatment of NPC patients. View Full-Text
Keywords: vitamin E; Niemann-Pick C; cholesterol; lysosomes; apoptosis; c-Abl vitamin E; Niemann-Pick C; cholesterol; lysosomes; apoptosis; c-Abl
Figures

This is an open access article distributed under the Creative Commons Attribution License (CC BY 3.0).

Scifeed alert for new publications

Never miss any articles matching your research from any publisher
  • Get alerts for new papers matching your research
  • Find out the new papers from selected authors
  • Updated daily for 49'000+ journals and 6000+ publishers
  • Define your Scifeed now

SciFeed Share & Cite This Article

MDPI and ACS Style

Marín, T.; Contreras, P.; Castro, J.F.; Chamorro, D.; Balboa, E.; Bosch-Morató, M.; Muñoz, F.J.; Alvarez, A.R.; Zanlungo, S. Vitamin E Dietary Supplementation Improves Neurological Symptoms and Decreases c-Abl/p73 Activation in Niemann-Pick C Mice. Nutrients 2014, 6, 3000-3017.

Show more citation formats Show less citations formats

Related Articles

Article Metrics

Article Access Statistics

1

Comments

[Return to top]
Nutrients EISSN 2072-6643 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert
Back to Top