Alteration of gene expressions by the overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mtPHGPx).
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.
Kitahara
Jun
J
Radioisotope Research Laboratory, Kitasato University, 5-9-1 Shirokane, Minato-ku, Tokyo 108-8641, Japan.
Chiba
Nobuyoshi
N
Sakamoto
Hikaru
H
Nakagawa
Yasuhito
Y
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
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