Differential activation of ERK and JNK by arsenite in mouse muscle cells.
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.
Ishrath
Ansurudeen
A
Signal Transduction Research Laboratory, Department of Biotechnology, National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, Punjab 160 062, India.
Kumar
Naresh
N
Dey
Chinmoy S
CS
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D018053:Arsenites / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D048031:JNK Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D051379:Mice; D020929:Mitogen-Activated Protein Kinase Kinases / Q000378:metabolism*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D009124:Muscle Proteins / Q000378:metabolism; D018482:Muscle, Skeletal / Q000187:drug effects / Q000201:enzymology*; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D016755:Proto-Oncogene Proteins c-jun / Q000502:physiology; D015398:Signal Transduction / Q000187:drug effects; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1
D018053:Arsenites; D004268:DNA-Binding Proteins; C494113:Elk1 protein, mouse; D009124:Muscle Proteins; D011518:Proto-Oncogene Proteins; D016755:Proto-Oncogene Proteins c-jun; D014157:Transcription Factors; D050807:ets-Domain Protein Elk-1; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D048670:MAP Kinase Kinase 4; D020929:Mitogen-Activated Protein Kinase Kinases; C015001:arsenite; D000111:Acetylcysteine