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18/09/2009Seminrios do Laboratrio de Controle do Metabolismo
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Factors that control the mass and function of skeletal muscleBASSEL-DUBY & OLSON. Annu Rev Biochem 75, 2006; NETTER. Atlas de anatomia humana, 2000.
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http://www.cellsignal.com/reference/pathway/images/Insulin_Receptor.jpgINSULIN
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SANDRI et al. Cell 117, 2004.
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http://www.cellsignal.com/reference/pathway/images/Insulin_Receptor.jpgINSULIN
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MAPK signaling pathwayshttp://www.babraham.ac.uk/images/research/signalling/cook/fig3a.jpg
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RAMOS et al. Int J Biochem Cell Biol 40, 2008.
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BUENO et al. EMBO 19(23): 6341-6350, 2000.MEK1 adenovirus induces anabolic status in cardiomyocytes
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MEK1 transgenic mice develops cardiac hypertrophyBUENO et al. EMBO 19(23): 6341-6350, 2000.
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Gastrocnemius treated for 2 weeks
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(+ ERK)(+ Akt)(+ ral)
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Examine the role of MAPK signaling in the maintenance of muscle mass in vitro and in vivo.
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RESULTS & DISCUSSION
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Inhibition of ERK1/2 signaling induced atrophy in myocytes
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Transcripton of atrophic markers muscle-specific E3-ligases in MAPK inhibition-induced myocyteIt parallels the preferential degradation of contractile proteins
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Cross talk between ERK and Akt signaling pathways
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Similar effect on Soleus muscle
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DISTINCT PROTEOLYTIC PATHWAYS DURING INHIBITION OF MAPK IN FAST AND SLOW MUSCLES
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ConclusionsERK1/2 inhibition-induced atrophy is caused by 3 distinct, yet related signaling pathways:
Reduction of protein synthesis at the transcription ans translational levels;
Downregulation of Akt and its downstream kinases;
Increase of 26S proteasome activity and gene expression of MuRF-1 and Atrogin-1.
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Clenbuterol increases the phosphorylation status of Akt and ERK p-Ser473 AktTotal Aktp-Thr202/Tyr204 ERK1p-Thr185/Tyr187 ERK2Total ERK1Total ERK2(p=0.07)(p=0.06)
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GONALVES et al. Endocrinology, 2009.
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Is cAMP responsible for phosphorylation status of Akt and ERK ?
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Formoterol increases the phosphorylation status of Akt and ERK p-Ser473 Akt-tubulinap-Thr202/Tyr204 ERK1p-Thr185/Tyr187 ERK2Total ERK1Total ERK2
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Obrigado!
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