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Evidence for down-regulation of phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR)-dependent translation regulatory signaling pathways in Ames dwarf mice.
- Source :
- Journals of Gerontology Series A: Biological Sciences & Medical Sciences; Mar2005, Vol. 60 Issue 3, p293-300, 8p, 5 Black and White Photographs, 1 Chart
- Publication Year :
- 2005
-
Abstract
- How growth hormone (GH) stimulates protein synthesis is unknown. Phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) signaling pathways balance anabolic and catabolic activities in response to nutrients and growth factor signaling. As a test of GH signaling, immunoassays of two downstream translation regulatory proteins were compared in ad libitum-fed 2-month-old normal and Ames (Prop1df) dwarf mice. Phosphorylation of the p70 and p85 isoforms of S6 kinase 1 in liver and the p70 isoform in gastrocnemius muscle were significantly decreased in dwarfs. Messenger RNA (mRNA) Cap-binding demonstrated significantly higher levels of translation repressor 4E-BP1/eukaryotic initiation factor 4E (eIF4E) (coprecipitates) from dwarf livers, but not muscle. Consistent with these binding data, significantly less phosphorylation of 4E-BP1 was documented in dwarf liver. These data suggest a link between GH signaling and translation control in a model of extended longevity. [ABSTRACT FROM AUTHOR]
- Subjects :
- SOMATOTROPIN
PROTEIN synthesis
PHOSPHOINOSITIDES
RAPAMYCIN
GENETIC translation
EUKARYOTIC cells
DWARFISM
AGING
ANIMAL experimentation
BIOCHEMISTRY
BIOLOGICAL models
CELLULAR signal transduction
COMPARATIVE studies
IMMUNOBLOTTING
LIVER
PHENOMENOLOGY
RESEARCH methodology
MEDICAL cooperation
MICE
PHOSPHORYLATION
RESEARCH
TISSUE culture
TRANSFERASES
GENETIC markers
EVALUATION research
HUMAN growth hormone
SKELETAL muscle
PHARMACODYNAMICS
PHYSIOLOGY
Subjects
Details
- Language :
- English
- ISSN :
- 10795006
- Volume :
- 60
- Issue :
- 3
- Database :
- Complementary Index
- Journal :
- Journals of Gerontology Series A: Biological Sciences & Medical Sciences
- Publication Type :
- Academic Journal
- Accession number :
- 17029053
- Full Text :
- https://doi.org/10.1093/gerona/60.3.293