INVESTIGADORES
MIQUET Johanna Gabriela
congresos y reuniones científicas
Título:
Role of PI3K/Akt and MAPK signaling pathways during the growth period in muscle of mice overexpressing growth hormone.
Autor/es:
PIAZZA VG; MARTINEZ CS; GONZÁLEZ L; TURYN D; MIQUET JG; SOTELO AI
Lugar:
San Carlos de Bariloche
Reunión:
Congreso; The Second South American Spring Symposium in Signal Transduction and Molecular Medicine (SISTAM); 2012
Institución organizadora:
Fundación de Ciencias Exactas y Naturales
Resumen:
Growth hormone (GH) promotes longitudinal body growth
acting mainly on liver, muscle and bone. It exerts its actions via its membrane
receptor which activates JAK2/STAT5, the main GH-signaling pathway related to
IGF-1 synthesis and body growth, PI3K/Akt/GSK3β and MEK/ERK1/2, both involved
in protein synthesis, cell survival and proliferation. Transgenic mice
overexpressing GH have higher circulating GH levels than normal mice since
birth, but no significant differences in body size are observed until the third
week of age. The aim of this work was to study the activation of PI3K/Akt/GSK3β
and MEK/ERK1/2 during the growth period in muscle of GH-transgenic mice to
investigate potential molecular mechanisms involved in the age-dependent growth
response to this hormone.
In order to evaluate mediators of these signaling
pathways, muscle was extracted from GH-transgenic mice and its normal siblings
of 2 weeks (GH-independent growth), 4 weeks (GH-dependent growth) and 9 weeks
old (young adult, control) and protein activation/content was assayed by
immunoblotting.
We observed higher protein levels of Akt and ERK1/2 in
pups compared to young adults. No difference was observed in GSK3β levels.
Activation of Akt and ERK1/2 decreased with age; there was no significant
difference between genotypes. GSK3β showed a different profile: its
phosphorylation was higher in 4 weeks transgenic mice respect to 2 and 9 weeks old
mice, whereas no difference was observed between normal mice.
In conclusion, the highest activation of these
signaling pathways is achieved during the GH-independent period of body growth,
in spite transgenic mice exhibit elevated levels of circulating GH throughout
life.