| First Author | Tsou HK | Year | 2010 |
| Journal | J Cell Biochem | Volume | 109 |
| Issue | 6 | Pages | 1244-53 |
| PubMed ID | 20135642 | Mgi Jnum | J:161245 |
| Mgi Id | MGI:4457835 | Doi | 10.1002/jcb.22508 |
| Citation | Tsou HK, et al. (2010) Integrin-linked kinase is involved in TNF-alpha-induced inducible nitric-oxide synthase expression in myoblasts. J Cell Biochem 109(6):1244-53 |
| abstractText | Tumor necrosis factor-alpha (TNF-alpha) is a pleiotropic cytokine produced by activated macrophages. Nitric oxide (NO) is a highly reactive nitrogen radical implicated in inflammatory responses. We investigated the signaling pathway involved in inducible nitric oxide synthase (iNOS) expression and NO production stimulated by TNF-alpha in cultured myoblasts. TNF-alpha stimulation caused iNOS expression and NO production in myoblasts (G7 cells). TNF-alpha-mediated iNOS expression was attenuated by integrin-linked kinase (ILK) inhibitor (KP392) and siRNA. Pretreatment with Akt inhibitor, mammalian target of rapamycin (mTOR) inhibitor (rapamycin), NF-kappaB inhibitor (PDTC), and IkappaB protease inhibitor (TPCK) also inhibited the potentiating action of TNF-alpha. Stimulation of cells with TNF-alpha increased ILK kinase activity. TNF-alpha also increased the Akt and mTOR phosphorylation. TNF-alpha mediated an increase of NF-kappaB-specific DNA-protein complex formation, p65 translocation into nucleus, NF-kappaB-luciferase activity was inhibited by KP392, Akt inhibitor, and rapamycin. Our results suggest that TNF-alpha increased iNOS expression and NO production in myoblasts via the ILK/Akt/mTOR and NF-kappaB signaling pathway. |
