title: Alteration of gene expressions by the overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mtPHGPx).
abstract: To determine the effect on gene expression of trace levels of reactive oxygen species from mitochondria, we used the mRNA differential display technique to compare gene expression in two cell lines: M15, which overexpresses mitochondrial phospholipid hydroperoxide glutathione peroxidase (mtPHGPx), in rat basophilic leukemia RBL-2H3 cells, and a control cell line, S1. We isolated 27 differentially expressed genes, including 10 previously unreported sequences. These genes included cytoskeletal proteins (beta-tubulin, nonmuscle myosin alkali light chain, and vimentin), growth or proliferation regulators [growth differentiation factor 1 (Gdf-1), Rap1a, and inhibitor of growth 3 (Ing3)], and others. Although the expression of most of the isolated genes did not respond to ROS (hydrogen peroxide) or antioxidant (pyrolidine dithiocarbamate) treatment, the expression of Gdf-1 was downregulated by hydrogen peroxide treatment. Thus, low levels of ROS produced in mitochondria during normal cellular metabolism can modulate gene expression.
authors.affiliation: Radioisotope Research Laboratory, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
authors.forename: Jun
authors.initials: J
authors.lastname: Kitahara
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Chiba
authors.forename: Hikaru
authors.initials: H
authors.lastname: Sakamoto
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Nakagawa
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D003598:Cytoskeletal Proteins / Q000235:genetics*; D015536:Down-Regulation; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D005979:Glutathione Peroxidase / Q000378:metabolism*; D055452:Growth Differentiation Factor 1; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008928:Mitochondria / Q000201:enzymology*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017382:Reactive Oxygen Species; D013859:Thiocarbamates / Q000494:pharmacology; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D000975:Antioxidants; D003598:Cytoskeletal Proteins; C525979:Gdf1 protein, rat; D055452:Growth Differentiation Factor 1; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D017382:Reactive Oxygen Species; D013859:Thiocarbamates; D006861:Hydrogen Peroxide; D000080662:Phospholipid Hydroperoxide Glutathione Peroxidase; D005979:Glutathione Peroxidase