| Grant number: | 13/18861-2 |
| Support type: | Regular Research Grants |
| Duration: | December 01, 2013 - November 30, 2015 |
| Field of knowledge: | Biological Sciences - Biochemistry |
| Principal Investigator: | Amanda Martins Baviera |
| Grantee: | Amanda Martins Baviera |
| Home Institution: | Faculdade de Ciências Farmacêuticas (FCFAR). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil |
| Assoc. researchers: | Iguatemy Lourenço Brunetti ; Isis Do Carmo Kettelhut ; Sílvia de Paula Gomes |
Abstract
It has been demonstrated that the inhibitory effect of catecholamines in the protein breakdown in skeletal muscles occurs, at least in part, through stimulation of beta2-adrenoceptors and increase in the intracellular levels of cyclic AMP (cAMP), involving the participation of two signaling cascades: i) an EPAC (Exchange protein directly activated by cAMP) dependent pathway, which leads to stimulation of AKT, inhibition of FoxO1/FoxO3a transcriptional factors and suppression of ubiquitin-proteasome system (UPS), and ii) a PKA-dependent pathway, which could decrease calcium-dependent proteolytic pathway. There is no study about the role of the cAMP signaling in the control of the caspase-mediated proteolysis, an intracellular process involved in both installation and maintenance of muscle atrophy; this process is essential for the dissociation of myofibrilar protein from sarcomere structure and subsequent offer of substrates for ubiquitination and degradation by the proteasome. Therefore, the association of i) a cAMP-dependent signaling that stimulates EPAC/AKT and inhibits FoxO1/FoxO3a, and ii) the participation of FoxO factors in the control of the caspase-mediated proteolysis, seems to be a promissory area of investigation. The understanding of the intracellular signals involved in the control of the caspase-mediated proteolysis will be useful to indicate important targets to the development of strategies in the control and/or reduction of muscle atrophy conditions. (AU)