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Seminários do Laboratório de Controle do Metabolismo

Seminários do Laboratório de Controle do Metabolismo. 18/09/2009. Neural. Hormonal. Nutritional. Factors that control the mass and function of skeletal muscle. BASSEL-DUBY & OLSON. Annu Rev Biochem 75, 2006; NETTER. Atlas de anatomia humana , 2000. INSULIN.

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Seminários do Laboratório de Controle do Metabolismo

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  1. Seminários do Laboratório de Controle do Metabolismo 18/09/2009

  2. Neural Hormonal Nutritional Factors that control the mass and function of skeletal muscle BASSEL-DUBY & OLSON. Annu Rev Biochem 75, 2006; NETTER. Atlas de anatomia humana, 2000.

  3. INSULIN http://www.cellsignal.com/reference/pathway/images/Insulin_Receptor.jpg

  4. Akt Akt-P SANDRI et al. Cell 117, 2004.

  5. INSULIN http://www.cellsignal.com/reference/pathway/images/Insulin_Receptor.jpg

  6. MAPK signaling pathways http://www.babraham.ac.uk/images/research/signalling/cook/fig3a.jpg

  7. RAMOS et al. Int J Biochem Cell Biol 40, 2008.

  8. MEK1 adenovirus induces anabolic status in cardiomyocytes BUENO et al. EMBO 19(23): 6341-6350, 2000.

  9. MEK1 transgenic mice develops cardiac hypertrophy BUENO et al. EMBO 19(23): 6341-6350, 2000.

  10. Gastrocnemius treated for 2 weeks

  11. (+ ERK) (+ Akt) (+ ral)

  12. Objective • Examine the role of MAPK signaling in the maintenance of muscle mass in vitro and in vivo.

  13. RESULTS & DISCUSSION

  14. Inhibition of ERK1/2 signaling induced atrophy in myocytes ERK1/2 inhibition p38 inhibition JNK inhibition

  15. ERK inhibitiondecreasescytosolicandcontractileproteins in myocytes

  16. Transcripton of atrophic markers muscle-specific E3-ligases in MAPK inhibition-induced myocyte It parallels the preferential degradation of contractile proteins

  17. Cross talk between ERK and Akt signaling pathways

  18. MyHC IIb  Similar effect on Soleus muscle

  19. Distinct proteolytic pathwaysduringinhibitionofmapk in fastandslowmuscles

  20. Conclusions • ERK1/2 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.

  21. Ourhypothesis...

  22. Clenbuterol increases the phosphorylation status of Akt and ERK (p=0.07) (p=0.06) p-Thr202/Tyr204 ERK1 p-Ser473 Akt p-Thr185/Tyr187 ERK2 Total ERK1 Total Akt Total ERK2

  23. Atrogin-1 Dynein MuRF-1 Dynein GONÇALVES et al. Endocrinology, 2009.

  24. Is cAMPresponsible for phosphorylation status ofAktand ERK ?

  25. Formoterol increases the phosphorylation status of Akt and ERK p-Thr202/Tyr204 ERK1 p-Ser473 Akt p-Thr185/Tyr187 ERK2 Total ERK1 α-tubulina Total ERK2

  26. Obrigado!

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