CL316,243, a selective β3-adrenoceptor agonist, activates protein translation through mTOR/p70S6K signaling pathway in rat skeletal muscle cells

Autor: Giuseppe Cirino, Rita Santamaria, Maria Concetta Miniaci, Mariarosaria Bucci, Pietro Scotto, Carlo Irace, Anna Cantalupo
Přispěvatelé: Miniaci, Maria, Bucci, Mariarosaria, Santamaria, Rita, Irace, Carlo, Cantalupo, Anna, Cirino, Giuseppe, P., Scotto
Rok vydání: 2013
Předmět:
Physiology
Muscle Fibers
Skeletal
Clinical Biochemistry
Gene Expression
Protein synthesi
Muscle hypertrophy
Propanolamines
Wortmannin
Phosphatidylinositol 3-Kinases
chemistry.chemical_compound
Pertussis toxin
Myocyte
Phosphorylation
p70S6K
Cells
Cultured
Phosphoinositide-3 Kinase Inhibitors
β2-Adrenoreceptor
Skeletal Muscle Myosins
TOR Serine-Threonine Kinases
Ribosomal Protein S6 Kinases
70-kDa
L6 cell
medicine.anatomical_structure
β3-Adrenoreceptor
mTOR
Signal transduction
Signal Transduction
Agonist
medicine.medical_specialty
medicine.drug_class
Adrenergic beta-Antagonists
Adrenergic beta-3 Receptor Agonists
Dioxoles
Biology
Skeletal muscle hypertrophy
Physiology (medical)
Internal medicine
medicine
Animals
Clenbuterol
PI3K/AKT/mTOR pathway
Sirolimus
CL316
Skeletal muscle
Actins
Rats
Androstadienes
Endocrinology
chemistry
Muscle ma
Protein Biosynthesis
Zdroj: Pflügers Archiv - European Journal of Physiology. 465:509-516
ISSN: 1432-2013
0031-6768
Popis: Functional β3-adrenoceptors have been found in skeletal muscle where they mediate metabolic oxidation and glucose utilization. Whether β3-adrenoceptors (ARs) also play any role in muscle protein metabolism still remains uncertain. By using rat L6 myocyte cultures, we found that CL316,243, a β3-AR selective agonist, at the concentration of 10(-6) M for 24 h, induced a significant increase of skeletal muscle constitutive proteins such as H- and L-myosin and β-actin. Such effect was correlated to an increased expression of phosphorylated p70(S6K) that was significantly inhibited by β3-AR antagonist, SR 59230A, but not by β2-AR antagonist, ICI-118,551. The CL316,243-induced activation of p70(S6K) was markedly inhibited by wortmannin, a PI3K inhibitor, and rapamycin, a specific inhibitor of mTOR, suggesting a critical involvement of the PI3K-mTOR-p70(S6K) signaling cascade in the anabolic response of L6 cells to β3-AR agonist. Taken together, these results suggest that stimulation of β3-AR in skeletal muscle cells activates a specific signaling pathway leading to protein synthesis and, eventually, muscle growth.
Databáze: OpenAIRE
Externí odkaz: