Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation

Treatment of murine myoblasts, myotubes and tumour cells with a tumour-prod uced lipid mobilizing factor (LMF), caused a concentration-dependent stimul ation of protein synthesis, within a 24 h period. There was no effect on ce ll number or [H-3] thymidine incorporation, but a similar concentation-depe ndent stimulation of 2-deoxyglucose uptake. LMF produced an increase in int racellular cyclic AMP levels, which was linearly (r(2) = 0.973) related to the increase in protein synthesis. The effect of LMF was attenuated by the adenylate cyclase inhibitor MDL12330A, and was additive with the stimulatio n produced by forskolin. Both propranolol (10 muM) and the specific beta (3 )-adrenergic receptor antagonist SR 59230A (10(-5)M), significantly reduced the stimulation of protein synthesis induced by LMF. Protein synthesis was also increased by 69% (P = 0.006) in soleus muscles of mice administered L MF, while there was a 26% decrease in protein degradation (P = 0.03). While LMF had no effect on the lysosomal enzymes, cathepsins B and L, there was a decrease in proteasome activity, as determined both by the 'chymofrypsin- like' enzyme activity as well as expression of proteasome a-type subunits, determined by Western blotting. These results show that in addition to ifs lipid-mobilizing activity LMF also increases protein accumulation in skelet al muscle both by an increase in protein synthesis and a decrease in protei n catabolism. (C) 2001 Cancer Research Campaign.