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 establis hed in C2C12 cells stably transfected with myotonin protein kinase (MtPK) c DNAs having 5, 46, 60, or 160 CTG repeats. The transformants showed CTG rep eat number-dependent susceptibility to oxidative stress. Mutant MtPK cDNA t ransformants 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 mild-type MtPK cDNA transformants, whereas mut ant MtPK cDNA transformants having 160 CTG repeats were defective in the in duction of the ERK pathway, although the activation of stress-activated pro tein 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 fo llowing oxidative stress. (C) 2000 Academic Press.