Produção Nacional
Revisado por pares
Serotonin stimulates mouse skeletal muscle 6-phosphofructo-1-kinase through tyrosine-phosphorylation of the enzyme altering its intracellular localization
2007; Elsevier BV; Volume: 92; Issue: 4 Linguagem: Inglês
10.1016/j.ymgme.2007.07.010
ISSN1096-7206
AutoresWagner Santos Coelho, Kelly Cristina Costa, Mauro Sola‐Penna,
Tópico(s)Metabolism, Diabetes, and Cancer
ResumoSerotonin (5-HT) is a hormone implicated in the regulation of many physiological and pathological events. One of its most intriguing properties is the ability to up-regulate mitosis. Moreover, it has been shown that 5-HT stimulate glucose uptake on skeletal muscle, suggesting that 5-HT may regulate glucose metabolism of peripheric tissues. Here we demonstrate that 5-HT stimulates skeletal muscle 6-phosphofructo-1-kinase (PFK) activity in a dose–response manner, through 5-HT2A receptor subtype. Maximal activation of the enzyme (2.5-fold compared to control) is achieved in the presence of 25 pM 5-HT, increasing both PFK maximal velocity and affinity for the substrate fructose-6-phosphate. These effects occur due to tyrosine phosphorylation of the enzyme that is 2-fold enhanced upon 5-HT stimulation of skeletal muscles preparation. Once 5-HT-induced tyrosine phosphorylation of PFK is prevented by genistein, a tyrosine kinase inhibitor, the hormone stimulatory effect on PFK is abrogated. Wortmannin, a phosphatidylinositol-3-kinase (PI3K) inhibitor, does not interfere on 5-HT-induced stimulation of PFK, supporting that the observed effects are independent on insulin signaling pathway. Furthermore, 5-HT promotes the association of PFK to the muscle f-actin, suggesting that the hormone alters PFK intracellular distribution, favoring its association to the cytoskeleton. Altogether, our results support evidences that 5-HT augments skeletal muscle glucose consumption through stimulation of glycolysis key regulatory enzyme, PFK, throughout tyrosine phosphorylation and intracellular redistribution of the enzyme.
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