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