Stimulation of Protein Degradation By Tumor Necrosis Factor a in Cultured Muscle Cells

The action of tumor necrosis factor a (TNF)/cachectin on the degradation of intracellular proteins was studied in cultured L6 myotubes. Cellular proteins were preliminarily labeled with [3H] tyrosine for either 18 hr (long-lived proteins, LLP) or 2 hr (short-lived proteins, SLP). Radiolabeled tyrosine released into the acid-soluble fraction of each experimental medium was used as an index of protein degradation. The degradation of LLP increased as the fetal calf serum (FCS) concentration was decreased from 10% to zero in the releasing medium TNF exerted no infulence on LLP degradation at any TNF concentration (0.2–20 ng/ml) nor at any FCS concentration (0–10%), nor over any action period (1–18 hr) of the cytokine. The degradation of SLP was also increased when the releasing medium was low in FCS. However, TNF was found to stimulate SLP degradation at concentrations of 0.2, 2 and 20 ng/ml when 10% FCS was contained in the releasing medium. These results suggest that TNF may stimulate the degradation of SLP in L6 myotubes in a direct manner when the basal rate of protein turnover in the myotubes is low. They also suggest that TNF cannot directly exert any influence on LLP degradation, even when the basal rate of protein turnover in the cells is low.