Effects of free nitrotyrosine on satellite cell lines and primary cultures?

GARNER M., LINICK C., RICART K.C., BRITTON B.M., VIERA L., BISIG G.C., A.G. ESTEVEZ.

San Diego, CA. USA

Congreso; Society for Neuroscience. 34 TH Annual Meeting; 2004

Amyotrophic Lateral Sclerosis is a neurodegenerative disorder characterized by the progressive degeneration of motor neurons in the brainstem, spinal cord, and motor cortex, which leads to paralysis of limb, bulbar, and respiratory muscles. Recent studies suggest that the cause of motor neuron degeneration may not be limited to abnormalities in motor neurons. Tumor necrosis factor alpha notably increases in concentration before the symptoms of disease arise in the spinal cord of transgenic mice for the G93A mutant SOD. We found that the concentration of TNFa also increases drastically in the same transgenic mice at the early stages of disease in the muscle. TNFa is known to induce the production of reactive nitrogen and oxygen species. Nitrotyrosine, a marker for the formation of reactive nitrogen species, induced a concentration-dependent inhibition of both proliferation and differentiation of G8 murine skeletal muscle cell line and primary cultures satellite cells from newborn and adult rats. In addition, conditioned media from differentiated G8 and primary satellite cell cultures incubated with nitrotyrosine induced motor neurons death, after the nitrotyrosine has been dialyzed out. We hypothesize that the muscles in ALS patients and animal models may be producing one or more products that might increase motor neuron vulnerability to noxious stimuli