Avtor/Urednik		Broussard, Suzanne R; McCusker, Robert H; Novakofski, Jan E; Strle, Klemen; Shen, Wen Hong; Johnson, Rodney W; Freund, Gregory G; Dantzer, Robert; Kelley, Keith W
Naslov		Cytokine-hormone interactions: tumor necrosis factor alpha impairs biologic activity and downstream activation signals of the insulin-like growth factor I receptor in myoblasts
Tip		članek
Vir		Endocrinology
Vol. in št.		Letnik 144, št. 7
Leto izdaje		2003
Obseg		str. 2988-96
Jezik		eng
Abstrakt		TNFalpha is elevated following damage to skeletal muscle. Here we provide evidence that TNFalpha acts on muscle cells to induce a state of IGF-I receptor resistance. We establish that TNFalpha inhibits IGF-I-stimulated protein synthesis in primary porcine myoblasts. Similar results were observed in C(2)C(12) murine myoblasts, where as little as 0.01 ng/ml TNFalpha significantly inhibits protein synthesis induced by IGF-I. TNFalpha also impairs the ability of IGF-I to induce expression of a key myogenic transcription factor, myogenin. The inhibition by TNFalpha of IGF-I-induced protein synthesis and expression of myogenin is not due to direct killing of myoblasts by TNFalpha. Although IGF-I induces an approximately 19-fold induction in tyrosine phosphorylation of the beta-chains of its receptor, TNFalpha does not inhibit this autophosphorylation. Instead, TNFalpha significantly reduces by approximately 50% IGF-I-stimulated tyrosine phosphorylation of two of the major downstream receptor docking molecules, insulin receptor substrate (IRS)-1 and IRS-2. These results establish that low picogram concentrations of TNFalpha acts on both porcine and murine myoblasts to impair tyrosine phosphorylation of both IRS-1 and IRS-2, but not the receptor itself. These data are consistent with the notion that very low physiological concentrations of TNFalpha interfere with both protein synthesis and muscle cell development by inducing a state of IGF-I receptor resistance.
Deskriptorji		ANIMALS ANTINEOPLASTIC AGENTS CELL DEATH MYOGENIN PHOSPHOPROTEINS PHOSPHORYLATION SIGNAL TRANSDUCTION SWINE TYROSINE