title: Omic analyses unravels global molecular changes in the brain and liver of a rat model for chronic Sake (Japanese alcoholic beverage) intake.
abstract: The effects of chronic administration of Sake (Japanese alcoholic beverage, Nihonshu) on brain and liver of female F334 (Fisher) rats were surveyed via global omic analyses using DNA microarray, 2-DE, and proton nuclear magnetic resonance. Rats weaned at 4 wk of age were given free access to Sake (15% alcohol), instead of water. At 13 months of age, and 24 h after withdrawal of Sake supply, rats were sacrificed, and the whole brain and liver tissues dissected for analyses. In general, molecular changes in brain were found to be less than those in liver. Transcriptomics data revealed 36 and 9, and 80 and 62 up- and down-regulated genes, in the brain and liver, respectively, with binding and catalytic activity gene categories the most prominently changed. Results suggested Sake-induced fragility of brain and liver toxicity/damage, though no significant abnormalities in growth were seen. At protein level, a striking decrease was found in the expression of NADH dehydrogenase (ubiquinone) Fe-S protein 1 in brain, suggesting attenuation of mitochondrial metabolism. In liver, results again suggested an attenuation of mitochondrial function and, in addition, glycoproteins with unknown function were induced at protein and gene levels, suggesting possible changes in glycoprotein binding in that organ. Metabolomic analysis of brain revealed significant increases in valine, arginine/ornithine, alanine, glutamine, and choline with decreases in isoleucine, N-acetyl aspartate, taurine, glutamate, and gamma aminobutyric acid. Our results provide a detailed inventory of molecular components of both brain and liver after Sake intake, and may help to better understand effects of chronic Sake drinking.
authors.affiliation: Health Technology Research Center (HTRC), National Institute of Advanced Industrial Science and Technology (AIST), Tsukuba, Japan.
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Masuo
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Imai
authors.forename: Junko
authors.initials: J
authors.lastname: Shibato
authors.forename: Misato
authors.initials: M
authors.lastname: Hirano
authors.forename: Oliver A H
authors.initials: OA
authors.lastname: Jones
authors.forename: Mahon L
authors.initials: ML
authors.lastname: Maguire
authors.forename: Kouji
authors.initials: K
authors.lastname: Satoh
authors.forename: Shoshi
authors.initials: S
authors.lastname: Kikuchi
authors.forename: Randeep
authors.initials: R
authors.lastname: Rakwal
mesh_terms: D056930:ARNTL Transcription Factors; D000434:Alcoholic Beverages; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D001923:Brain Chemistry / Q000187:drug effects; D015180:Electrophoresis, Gel, Two-Dimensional; D000431:Ethanol / Q000008:administration & dosage / Q000494:pharmacology*; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D007564:Japan; D008099:Liver / Q000737:chemistry* / Q000187:drug effects; D055432:Metabolomics; D015999:Multivariate Analysis; D009245:NADH Dehydrogenase; D019906:Nuclear Magnetic Resonance, Biomolecular; D020411:Oligonucleotide Array Sequence Analysis; D018384:Oxidative Stress; D011247:Pregnancy; D040901:Proteomics; D051381:Rats; D011916:Rats, Inbred F344; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction
chemical_list: D056930:ARNTL Transcription Factors; D051792:Basic Helix-Loop-Helix Proteins; D000431:Ethanol; D009245:NADH Dehydrogenase