TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes
TNF-α was shown to stimulate mitogenicity in C2C12 myoblasts. Selected cytokines TNF-α, IFNα, or IFNγ reduced the expression of myosin heavy chain (MyHC IIa) when given together. Molecular mechanisms of cytokine activities were controlled by NF-κB and JAK/STAT signaling pathways, as metabolic inhibi...
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| Format: | Article |
| Language: | English |
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Wiley
2013-01-01
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| Series: | Mediators of Inflammation |
| Online Access: | http://dx.doi.org/10.1155/2013/171437 |
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| author | Barbara Pijet Maja Pijet Anna Litwiniuk Małgorzata Gajewska Beata Pająk Arkadiusz Orzechowski |
| author_facet | Barbara Pijet Maja Pijet Anna Litwiniuk Małgorzata Gajewska Beata Pająk Arkadiusz Orzechowski |
| author_sort | Barbara Pijet |
| collection | DOAJ |
| description | TNF-α was shown to stimulate mitogenicity in C2C12 myoblasts. Selected cytokines TNF-α, IFNα, or IFNγ reduced the expression of myosin heavy chain (MyHC IIa) when given together. Molecular mechanisms of cytokine activities were controlled by NF-κB and JAK/STAT signaling pathways, as metabolic inhibitors, curcumin and AG490, inhibited some of TNF-α and IFNα/IFNγ effects. Insulin was hardly antagonistic to TNF-α- and IFNα/IFNγ-dependent decrease in MyHC IIa protein expression. Cytokines used individually or together also repressed myogenesis of C2C12 cells. Moreover, TNF-α- and IFNα/IFNγ-dependent effects on C2C12 myotubes were associated with increased activity of Atrogin1 and MuRF1 genes, which code ubiquitin ligases. MyHC IIa gene activity was unaltered by cytokines. Inhibition of NF-κB or JAK/STAT with specific metabolic inhibitors decreased activity of Atrogin1 and MuRF1 but not MyHC IIa gene. Overall, these results suggest cooperation between cytokines in the reduction of MyHC IIa protein expression level via NF-κB/JAK/STAT signaling pathways and activation of Atrogin1 and MuRF1 genes as their molecular targets. Insulin cotreatment or pretreatment does not protect against muscle decay induced by examined proinflammatory cytokines. |
| format | Article |
| id | doaj-art-a83744159f9b407d914778dc6fbc280f |
| institution | OA Journals |
| issn | 0962-9351 1466-1861 |
| language | English |
| publishDate | 2013-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Mediators of Inflammation |
| spelling | doaj-art-a83744159f9b407d914778dc6fbc280f2025-08-20T02:20:44ZengWileyMediators of Inflammation0962-93511466-18612013-01-01201310.1155/2013/171437171437TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 MyotubesBarbara Pijet0Maja Pijet1Anna Litwiniuk2Małgorzata Gajewska3Beata Pająk4Arkadiusz Orzechowski5Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, PolandDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, PolandDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, PolandDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, PolandElectron Microscopy Platform, Mossakowski Medical Research Centre, Polish Academy of Sciences, Pawińskiego 5, 02-106 Warsaw, PolandDepartment of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences—SGGW, Nowoursynowska 159, 02-776 Warsaw, PolandTNF-α was shown to stimulate mitogenicity in C2C12 myoblasts. Selected cytokines TNF-α, IFNα, or IFNγ reduced the expression of myosin heavy chain (MyHC IIa) when given together. Molecular mechanisms of cytokine activities were controlled by NF-κB and JAK/STAT signaling pathways, as metabolic inhibitors, curcumin and AG490, inhibited some of TNF-α and IFNα/IFNγ effects. Insulin was hardly antagonistic to TNF-α- and IFNα/IFNγ-dependent decrease in MyHC IIa protein expression. Cytokines used individually or together also repressed myogenesis of C2C12 cells. Moreover, TNF-α- and IFNα/IFNγ-dependent effects on C2C12 myotubes were associated with increased activity of Atrogin1 and MuRF1 genes, which code ubiquitin ligases. MyHC IIa gene activity was unaltered by cytokines. Inhibition of NF-κB or JAK/STAT with specific metabolic inhibitors decreased activity of Atrogin1 and MuRF1 but not MyHC IIa gene. Overall, these results suggest cooperation between cytokines in the reduction of MyHC IIa protein expression level via NF-κB/JAK/STAT signaling pathways and activation of Atrogin1 and MuRF1 genes as their molecular targets. Insulin cotreatment or pretreatment does not protect against muscle decay induced by examined proinflammatory cytokines.http://dx.doi.org/10.1155/2013/171437 |
| spellingShingle | Barbara Pijet Maja Pijet Anna Litwiniuk Małgorzata Gajewska Beata Pająk Arkadiusz Orzechowski TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes Mediators of Inflammation |
| title | TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes |
| title_full | TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes |
| title_fullStr | TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes |
| title_full_unstemmed | TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes |
| title_short | TNF-α and IFN-s-Dependent Muscle Decay Is Linked to NF-κB- and STAT-1α-Stimulated Atrogin1 and MuRF1 Genes in C2C12 Myotubes |
| title_sort | tnf α and ifn s dependent muscle decay is linked to nf κb and stat 1α stimulated atrogin1 and murf1 genes in c2c12 myotubes |
| url | http://dx.doi.org/10.1155/2013/171437 |
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