title: Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats.
abstract: The recent discovery that vitamin E (VE) regulates gene activity at the transcriptional level indicates that VE may exert part of its biological effects by mechanisms which may be independent of its well-recognised antioxidant function. The objective of this study was the identification of hepatic vitamin E-sensitive genes and examination of the effects of VE on their corresponding biological endpoints. Two groups of male rats were randomly assigned to either a VE-sufficient diet or to a control diet deficient in VE for 290 days. High-density oligonucleotide microarrays comprising over 7000 genes were used to assess the transcriptional response of the liver. Differential gene expression was monitored over a period of 9 months, at four different time-points, and rats were individually profiled. This experimental strategy identified several VE-sensitive genes, which were chronically altered by dietary VE. VE supplementation down-regulated scavenger receptor CD36, coagulation factor IX and 5-alpha-steroid reductase type 1 mRNA levels while hepatic gamma glutamyl-cysteinyl synthetase was significantly up-regulated. Measurement of the corresponding biological endpoints such as activated partial thromboplastin time, plasma dihydrotestosterone and hepatic glutathione substantiated the gene chip data which indicated that dietary VE plays an important role in a range of metabolic processes within the liver.
authors.affiliation: DSM Nutritional Products (registered as Roche Vitamins Ltd), Human Nutrition and Health, P O Box 3255, CH-4002 Basel, Switzerland.
authors.forename: Luca
authors.initials: L
authors.lastname: Barella
authors.forename: Patrick Y
authors.initials: PY
authors.lastname: Muller
authors.forename: Manfred
authors.initials: M
authors.lastname: Schlachter
authors.forename: Willi
authors.initials: W
authors.lastname: Hunziker
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Stöcklin
authors.forename: Volker
authors.initials: V
authors.lastname: Spitzer
authors.forename: Nina
authors.initials: N
authors.lastname: Meier
authors.forename: Sonia
authors.initials: S
authors.lastname: de Pascual-Teresa
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Minihane
authors.forename: Gerald
authors.initials: G
authors.lastname: Rimbach
mesh_terms: D000821:Animal Feed; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D018955:CD36 Antigens; D005164:Factor IX / Q000235:genetics; D020869:Gene Expression Profiling; D005721:Glutamate-Cysteine Ligase / Q000235:genetics; D005978:Glutathione / Q000378:metabolism; D008099:Liver / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D011770:Pyruvate Kinase / Q000097:blood / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D011971:Receptors, Immunologic / Q000235:genetics; D051116:Receptors, Scavenger; D013997:Time Factors; D024502:alpha-Tocopherol / Q000008:administration & dosage / Q000097:blood / Q000494:pharmacology*
chemical_list: D018955:CD36 Antigens; D012333:RNA, Messenger; D011971:Receptors, Immunologic; D051116:Receptors, Scavenger; D005164:Factor IX; D011770:Pyruvate Kinase; D005721:Glutamate-Cysteine Ligase; D005978:Glutathione; D024502:alpha-Tocopherol