Expanded CTG repeats in myotonin protein kinase increase susceptibility to oxidative stress.
The effect of oxidative stress on myogenic cells with expanded CTG repeats in the myotonin protein kinase (MtPK) gene was investigated using MtPK cDNA-transformants in order to investigate the disease process underlying myotonic dystrophy. We employed methylmercury as a model for reagents that produce reactive oxygen species (ROS). Mutant MtPK cDNA transformants containing 46 CTG repeats treated with 1 microM methylmercury for 24 h underwent cell death showing the characteristics of apoptosis. In contrast, methylmercury-induced cytotoxicity was weaker in wild type MtPK cDNA transformants. Antioxidants such as N-acetyl-L-cysteine and trolox suppressed methylmercury-induced apoptosis, indicating that the intracellular generation of ROS plays an important role. These studies suggest that expanded CTG repeats in MtPK increase the susceptibility of cells to oxidative stress.
Department of Clinical Medicine, National Institute for Minamata Disease, Hama, Japan.
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Usuki
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Ishiura
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D053938:DNA Fragmentation / Q000187:drug effects; D006801:Humans; D008767:Methylmercury Compounds / Q000633:toxicity; D009223:Myotonic Dystrophy / Q000503:physiopathology; D065636:Myotonin-Protein Kinase; D009707:Nucleosomes / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics*; D011494:Protein Kinases / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases; D017382:Reactive Oxygen Species / Q000378:metabolism; D014162:Transfection; D018911:Trinucleotide Repeats / Q000235:genetics*
D000975:Antioxidants; C585517:DMPK protein, human; D008767:Methylmercury Compounds; D009707:Nucleosomes; D017382:Reactive Oxygen Species; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases