Printen
Glutahion herstelt spiermassa bij chronische onstekingen.*
Nieuw onderzoek laat zien dat door optimale Glutathion
waarden te handhaven de spiermassa hersteld wordt bij chronische
onstekingsprocessen.
Glutathione Depletion Impairs
Myogenic Differentiation of Murine Skeletal Muscle C2C12 Cells through Sustained
NF-
kappaB
Activation
Esther
Ardite*, Joan Albert Barbera*, Josep Roca* and
Jose C. Fernández-Checa
From the Servei de
Pneumologia,* Instituto Clinic de Pneumologia y Cirugía Torácica,
Barcelona; Liver Unit,
Instituto Malalties Digestives, Hospital Clinic i Provincial,
Instituto Investigaciones Biomedicas August Pi i Sunyer, Barcelona; and
Department of Experimental Pathology,
Instituto Investigaciones Biomédicas de Barcelona, Consejo Superior
Investigaciones Científicas, Barcelona, Spain
Skeletal muscle differentation is a complex process regulated at multiple levels. This study addressed the effect of glutathione (GSH) depletion on the transition of murine skeletal muscle C2C12 myoblasts into myocytes induced by growth factor inactivation. Cellular GSH levels increased within 24 hours on myogenic stimulation of myoblasts due to enhanced GSH synthetic rate accounted for by stimulated glutamate-L-cysteine ligase (also known as -glutamylcysteine synthetase) activity. In contrast, the synthesis rate of GSH using -glutamylcysteine and glutamate as precursors, which reflects the activity of the GSH synthetase, did not change during differentiation. The stimulation of GSH stores preceded the myogenic differentiation of C2C12 myoblasts monitored by expression of muscle-specific genes, creatine kinase (CK), myosin heavy chain (MyHC), and MyoD. The pattern of DNA binding activity of NF- kappaB and AP-1 in differentiating cells was similar both displaying an activation peak at 24 hours after myogenic stimulation. Depletion of cellular GSH levels 24 hours after stimulation of differentiation abrogated myogenesis as reflected by lower CK activity, MyHC levels, MyoD expression, and myotubes formation, effects that were reversible on GSH replenishment by GSH ethyl ester (GHSEE). Moreover, GSH depletion led to sustained activation of NF- kappaB, while GSHEE prevented it. Furthermore, inhibition of NF-kappaB activation restored myogenesis despite GSH depletion. Thus, GSH contributes to the formation of myotubes from satellite myoblasts by ensuring inactivation of NF- kappaB, and hence maintaining optimal GSH levels may be beneficial in restoring muscle mass in chronic inflammatory disorders.(American Journal of Pathology, 2004; 165:719-728)