PCR-verified microarray analysis and functional in vitro studies indicate a role of alpha-tocopherol in vesicular transport.
Global gene expression profiles of livers from mice, fed diets differing in alpha-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 alpha-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, alpha-tocopherol increased the secretory response in RBL and PC12 cells. Although here detected in liver, the alpha-tocopherol-responsive pathways are also relevant to neurotransmission. A role of alpha-tocopherol in the vesicular transport might not only affect its own absorption and transport but also explain the neural dysfunctions observed in severe alpha-tocopherol deficiency.
Nell
Sandra
S
German Institute of Human Nutrition Potsdam-Rehbrücke, Nuthetal, Germany.
Bahtz
Ramona
R
Bossecker
Anja
A
Kipp
Anna
A
Landes
Nico
N
Bumke-Vogt
Christiane
C
Halligan
Eugene
E
Lunec
Joseph
J
Brigelius-Flohé
Regina
R
D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage* / Q000032:analysis; D001692:Biological Transport / Q000235:genetics; D004032:Diet; D020869:Gene Expression Profiling; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D022161:Transport Vesicles / Q000235:genetics*; D024502:alpha-Tocopherol / Q000008:administration & dosage* / Q000032:analysis
D000975:Antioxidants; D024502:alpha-Tocopherol