Effect of a tumour-produced lipid-mobilizing factor on protein synthesis and degradation.
Treatment of murine myoblasts, myotubes and tumour cells with a tumour-produced lipid mobilizing factor (LMF), caused a concentration-dependent stimulation of protein synthesis, within a 24 h period. There was no effect on cell number or [(3)H] thymidine incorporation, but a similar concentration-dependent stimulation of 2-deoxyglucose uptake. LMF produced an increase in intracellular 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 MDL(12330A), and was additive with the stimulation produced by forskolin. Both propranolol (10 microM) 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 LMF, 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 'chymotrypsin-like' enzyme activity, as well as expression of proteasome alpha-type subunits, determined by Western blotting. These results show that in addition to its lipid-mobilizing activity LMF also increases protein accumulation in skeletal muscle both by an increase in protein synthesis and a decrease in protein catabolism.
Islam-Ali
B S
BS
Pharmaceutical Sciences Research Institute, Aston University, Birmingham B4 7ET, UK.
Tisdale
M J
MJ
D000818:Animals; D015153:Blotting, Western; D002100:Cachexia / Q000503:physiopathology*; D000242:Cyclic AMP / Q000378:metabolism; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism*; D010766:Phosphorylation; D014176:Protein Biosynthesis; D011943:Receptors, Adrenergic, beta / Q000502:physiology; D013936:Thymidine; D014407:Tumor Cells, Cultured
D011943:Receptors, Adrenergic, beta; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D013936:Thymidine