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

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.