Differential signaling pathways following oxidative stress in mutant myotonin protein kinase cDNA-transfected C2C12 cell lines.
We investigated the response to oxidative stress in a model system established in C2C12 cells stably transfected with myotonin protein kinase (MtPK) cDNAs having 5, 46, 60, or 160 CTG repeats. The transformants showed CTG repeat number-dependent susceptibility to oxidative stress. Mutant MtPK cDNA transformants containing 160 CTG repeats showed apoptotic cell death by the exposure to an oxidant, a very low level of methylmercury. The addition of the antioxidant Trolox protected transformants against apoptosis. Oxidative stress activated the extracellular signal-regulated kinases (ERKs) pathway leading to cell survival in wild-type MtPK cDNA transformants, whereas mutant MtPK cDNA transformants having 160 CTG repeats were defective in the induction of the ERK pathway, although the activation of stress-activated protein kinase (SAPK)/c-Jun N-terminal kinase (JNK) was strong and sustained. These results suggest that the susceptibility to oxidative stress in mutant MtPK cDNA transformants involves differential signaling pathways evoked following oxidative stress.
Usuki
F
F
Department of Clinical Medicine, National Institute for Minamata Disease, 4058-18 Hama, Minamata, 867-0008, Japan. usuki@nimd.go.jp
Takahashi
N
N
Sasagawa
N
N
Ishiura
S
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D018076:DNA, Complementary; D006801:Humans; D048031:JNK Mitogen-Activated Protein Kinases; D008767:Methylmercury Compounds / Q000494:pharmacology; D051379:Mice; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D018482:Muscle, Skeletal; D009223:Myotonic Dystrophy; D065636:Myotonin-Protein Kinase; D018384:Oxidative Stress; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology*; D014162:Transfection
D000975:Antioxidants; C585517:DMPK protein, human; C585516:DMPK protein, mouse; D018076:DNA, Complementary; D008767:Methylmercury Compounds; D011994:Recombinant Proteins; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; C004925:methylmercuric chloride