Differential activation of ERK and JNK by arsenite in mouse muscle cells

Abstract

We studied the activation of MAPKs, such as ERK and JNK, by arsenite in C2C12 mouse skeletal muscle cells as a function of proliferation and differentiation. Data showed that both ERK and JNK were activated by arsenite in proliferated and differentiated cells in a differential manner. The activation of the enzymes was not due to alteration in their concentration. The activities were independent of each other. ERK activation was possibly partly through the activity of Ras, Raf and the MEK cascade, and due to oxidative stress, which possibly led to the activation of the transcription factor, Elk-1. In contrast, the activation of JNK was solely due to the generation of free radicals, resulting in activation of c-Jun and perhaps Elk-1. These results show for the first time that, in skeletal muscle, stress caused by arsenite involves the MAP-kinase signal transduction cascade, perhaps in a cell type-specific regulatory pathway.