Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats

Barella, Luca, Muller, Patrick Y, Schlachter, Manfred, Hunziker, Willi, Stöcklin, Elisabeth, Spitzer, Volker, Meier, Nina, de Pascual-Teresa, Sonia, Minihane, Anne Marie ORCID: https://orcid.org/0000-0001-9042-4226 and Rimbach, Gerald (2004) Identification of hepatic molecular mechanisms of action of alpha-tocopherol using global gene expression profile analysis in rats. Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease, 1689 (1). pp. 66-74.

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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-α-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.

Item Type: Article
Faculty \ School: Faculty of Medicine and Health Sciences > Norwich Medical School
UEA Research Groups: Faculty of Medicine and Health Sciences > Research Groups > Nutrition and Preventive Medicine
Faculty of Medicine and Health Sciences > Research Groups > Cardiovascular and Metabolic Health
Faculty of Medicine and Health Sciences > Research Centres > Lifespan Health
Depositing User: Rhiannon Harvey
Date Deposited: 01 Jun 2011 08:48
Last Modified: 19 Oct 2023 00:56
URI: https://ueaeprints.uea.ac.uk/id/eprint/31654
DOI: 10.1016/j.bbadis.2004.02.002

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