PCR-verified microarray analysis and functional in vitro studies indicate a role of α-tocopherol in vesicular transport

Authors: Nell, Sandra1; Bahtz, Ramona1; Boßecker, Anja1; Kipp, Anna1; Landes, Nico1; Bumke-Vogt, Christiane1; Halligan, Eugene2; Lunec, Joseph2; Brigelius-Flohé, Regina1

Source: Free Radical Research, Volume 41, Number 8, 2007 , pp. 930-942(13)

Publisher: Informa Healthcare

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Abstract:

Global gene expression profiles of livers from mice, fed diets differing in α-tocopherol content, were compared using DNA microarray technology. Three hundred and eighty nine genes were found to significantly differ in their expression level by a factor of 2 or higher between the high and the low α-tocopherol group. Functional clustering using the EASE software identified 121 genes involved in transport processes. Twenty-one thereof were involved in (synaptic) vesicular trafficking. Up-regulation of syntaxin 1C (Stx1c), vesicle-associated membrane protein 1 (Vamp1), N-ethylmaleimide-sensitive factor (Nsf) and syntaxin binding protein 1 (Stxbp1, Munc18-1) was verified by real time PCR. At a functional level, α-tocopherol increased the secretory response in RBL and PC12 cells. Although here detected in liver, the α-tocopherol-responsive pathways are also relevant to neurotransmission. A role of α-tocopherol in the vesicular transport might not only affect its own absorption and transport but also explain the neural dysfunctions observed in severe α-tocopherol deficiency.

Keywords: α-tocopherol; endocytosis; gene regulation; vesicular transport; exocytosis

Document Type: Research article

DOI: http://dx.doi.org/10.1080/10715760701416988

Affiliations: 1: German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany 2: Molecular Toxicology, Pharmaceutical Sciences, Kings College, London, UK

Publication date: 2007-01-01

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