EXPANDED CTG REPEATS IN MYOTONIN PROTEIN-KINASE INCREASE SUSCEPTIBILITY TO OXIDATIVE STRESS

THE effect of oxidative stress on myogenic cells with expanded CTG rep eats in the myotonin protein kinase (MtPK) gene was investigated using MtPK cDNA-transformants in order to investigate the disease process u nderlying 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 mu M methylmer cury for 24 h underwent cell death showing the characteristics of apop tosis. In contrast, methylmercury-induced cytotoxicity was weaker in w ild type MtPK cDNA transformants. Antioxidants such as N-acetyl-L-cyst eine and trolox suppressed methylmercury-induced apoptosis, indicating that the intracellular generation of ROS plays an important role. The se studies suggest that expanded CTG repeats in MtPK increase the susc eptibility of cells to oxidative stress. NeuroReport 9: 2291-2296 (C) 1998 Rapid Science Ltd.