title: The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice.
abstract: The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05% Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p<0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.
authors.affiliation: 1 Asai Germanium Research Institute Co., Ltd., Hakodate, Hokkaido, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Nakamura
authors.forename: Tomoya
authors.initials: T
authors.lastname: Takeda
authors.forename: Yoshihiko
authors.initials: Y
authors.lastname: Tokuji
mesh_terms: D000818:Animals; D000975:Antioxidants; D001647:Bile Acids and Salts / Q000235:genetics / Q000378:metabolism; D001663:Bilirubin / Q000235:genetics; D004032:Diet; D005857:Germanium / Q000008:administration & dosage*; D007109:Immunity / Q000187:drug effects*; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D020411:Oligonucleotide Array Sequence Analysis / Q000662:veterinary; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017392:Thiobarbituric Acid Reactive Substances / Q000032:analysis; D059467:Transcriptome / Q000187:drug effects*; D024502:alpha-Tocopherol / Q000097:blood*
chemical_list: D000975:Antioxidants; D001647:Bile Acids and Salts; D017392:Thiobarbituric Acid Reactive Substances; D005857:Germanium; D024502:alpha-Tocopherol; D001663:Bilirubin
keywords: gene expression; immune modulation; microarray; organic germanium; tocopherol transfer protein