Grefte 2015 Biochim Biophys Acta: Difference between revisions
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{{Publication | {{Publication | ||
|title=Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ (2015) Rotenone inhibits primary murine myotube formation via Raf-1 and ROCK2. Biochim Biophys Acta 1853:1606-14. ย | |title=Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ (2015) Rotenone inhibits primary murine myotube formation via Raf-1 and ROCK2. Biochim Biophys Acta 1853:1606-14. | ||
|info=[http://www.ncbi.nlm.nih.gov/pubmed/25827955 PMID: 25827955] | |info=[http://www.ncbi.nlm.nih.gov/pubmed/25827955 PMID: 25827955] | ||
|authors=Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ | |authors=Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ | ||
|year=2015 | |year=2015 | ||
|journal=Biochim Biophys Acta | |journal=Biochim Biophys Acta | ||
|abstract=Rotenone ( | |abstract=Rotenone (Rot) is a widely used inhibitor of Complex I (CI), the first complex of the mitochondrial oxidative phosphorylation (OXPHOS) system. However, particularly at high concentrations Rot was also described to display off-target effects. Here we studied how Rot affected ''in vitro'' primary murine myotube formation. We demonstrate that myotube formation is specifically inhibited by Rot (10-100 nM), but not by piericidin A (PA; 100 nM), another CI inhibitor. At 100 nM, both Rot and PA fully blocked myoblast oxygen consumption. Knock-down of Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) and, to a lesser extent ROCK1, prevented the Rot-induced inhibition of myotube formation. Moreover, the latter was reversed by inhibiting Raf-1 activity. In contrast, Rot-induced inhibition of myotube formation was not prevented by knock-down of RhoA. Taken together, our results support a model in which Rot reduces primary myotube formation independent of its inhibitory effect on CI-driven mitochondrial ATP production, but via a mechanism primarily involving the Raf-1/ROCK2 pathway. | ||
|keywords=Fusion index, GW5074, U0126, Rotenone, Piericidin A, Rho-GTPase | |keywords=Fusion index, GW5074, U0126, Rotenone, Piericidin A, Rho-GTPase | ||
|mipnetlab=NL Nijmegen Koopman WJ | |||
}} | }} | ||
{{Labeling | {{Labeling | ||
|area=Respiration | |||
|organism=Mouse | |organism=Mouse | ||
|tissues=Skeletal muscle | |tissues=Skeletal muscle, Other cell lines | ||
|preparations=Intact cells | |||
|preparations= | |topics=Inhibitor | ||
|topics= | |||
|couplingstates=ROUTINE | |couplingstates=ROUTINE | ||
|instruments=Oxygraph-2k | |instruments=Oxygraph-2k | ||
}} | }} |
Latest revision as of 10:43, 9 November 2016
Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ (2015) Rotenone inhibits primary murine myotube formation via Raf-1 and ROCK2. Biochim Biophys Acta 1853:1606-14. |
Grefte S, Wagenaars JA, Jansen R, Willems PH, Koopman WJ (2015) Biochim Biophys Acta
Abstract: Rotenone (Rot) is a widely used inhibitor of Complex I (CI), the first complex of the mitochondrial oxidative phosphorylation (OXPHOS) system. However, particularly at high concentrations Rot was also described to display off-target effects. Here we studied how Rot affected in vitro primary murine myotube formation. We demonstrate that myotube formation is specifically inhibited by Rot (10-100 nM), but not by piericidin A (PA; 100 nM), another CI inhibitor. At 100 nM, both Rot and PA fully blocked myoblast oxygen consumption. Knock-down of Rho-associated, coiled-coil containing protein kinase 2 (ROCK2) and, to a lesser extent ROCK1, prevented the Rot-induced inhibition of myotube formation. Moreover, the latter was reversed by inhibiting Raf-1 activity. In contrast, Rot-induced inhibition of myotube formation was not prevented by knock-down of RhoA. Taken together, our results support a model in which Rot reduces primary myotube formation independent of its inhibitory effect on CI-driven mitochondrial ATP production, but via a mechanism primarily involving the Raf-1/ROCK2 pathway. โข Keywords: Fusion index, GW5074, U0126, Rotenone, Piericidin A, Rho-GTPase
โข O2k-Network Lab: NL Nijmegen Koopman WJ
Labels: MiParea: Respiration
Organism: Mouse
Tissue;cell: Skeletal muscle, Other cell lines
Preparation: Intact cells
Regulation: Inhibitor Coupling state: ROUTINE
HRR: Oxygraph-2k