title: Growth factor and cytokine interactions in myogenesis. Part II. Expression of IGF binding proteins and protein kinases essential for myogenesis in mouse C2C12 myogenic cells exposed to TNF-alpha and IFN-gamma.
abstract: The aim of the study was to examine potential interactions among IGF-I and proinflammatory cytokines, TNF-alpha and IFN-gamma, in the regulation of local IGF-I bioavailability and cellular proteins mediating myogenic signals. We investigated levels of IGFBP-4, -5, -6, protein kinase Czeta (PKC zeta), p38 and extracellular signal-regulated kinase (ERK1/2) in differentiating mouse C2C12 myoblasts. IGF-I significantly stimulated expression of IGFBP-5. TNF-alpha and IFN-gamma attenuated the expression of IGFBP-4 and -6 under basal conditions and in the presence of IGF-I, and inhibited IGF-I-induced IGFBP-5 expression during 5-day myogenesis. TNF-alpha and IFN-gamma markedly attenuated p38 expression in the presence of IGF-I on the 5th day of myogenesis. When combined with IGF-I the cytokines exerted opposite effects on the PKC zeta level, i.e. TNF-alpha caused an increase, whereas IFN-gamma reduced the cellular content of this kinase. Exposition of C2C12 myoblasts to IGF-I or cytokines led to the stimulation of ERK1/2 phosphorylation; however, both TNF-alpha and IFN-gamma exerted an inhibitory effect on the activation of ERK1/2 in myoblasts cultured in the presence of IGF-I. We concluded as follows: i) TNF-alpha and IFN-gamma present in the extracellular environment of differentiating C2C12 myoblasts can alter the local bioavailability of IGF-I by inhibiting the expression of IGFBP-4, -5, and -6, ii) the decrease in p38 expression and ERK1/2 phosphorylation in C2C12 myoblasts exposed to cytokines can lead to disturbances in IGF-I-regulated myogenesis.
authors.affiliation: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (SGGW), Nowoursynowska 159, 02-776 Warsaw, Poland.
authors.forename: W
authors.initials: W
authors.lastname: Wieteska-Skrzeczyńska
authors.forename: K
authors.initials: K
authors.lastname: Grzelkowska-Kowalczyk
authors.forename: E
authors.initials: E
authors.lastname: Rejmak
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology*; D051379:Mice; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development; D032446:Myoblasts / Q000187:drug effects* / Q000378:metabolism*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
chemical_list: D018969:Insulin-Like Growth Factor Binding Proteins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D011494:Protein Kinases