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Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling.
Horm Metab Res. 2013 Mar; 45(3):183-9.HM

Abstract

The molecular mechanisms by which cellular energy status regulates global protein synthesis in mammary epithelial cells have not been characterized. The objective of this study was to examine the effect of AMP-activated protein kinase (AMPK) activation by 2-deoxyglucose on protein synthesis and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in bovine mammary epithelial cells. Phosphorylation of AMPK at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to 2-deoxyglucose. Global rates of protein synthesis declined by 78% of control values. The decline in protein synthesis was associated with repression of mTORC1 signaling, as indicated by reduced phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein-1 (4E-BP1). Phosphorylation of ER-stress marker eIF2α was also increased but only at 30 min of 2-deoxyglucose exposure. 2-Deoxyglucose increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2. Activation of AMPK did not result in changes in the amount of raptor bound to mTOR. The inhibitory effects of AMPK activation on mTORC1 signaling were associated with a marked increase in Ser792 phosphorylation on raptor. Collectively, the results suggest that activation of AMPK represses global protein synthesis in mammary epithelial cells through inhibition of mTORC1 signaling.

Authors+Show Affiliations

Department of Animal and Poultry Science, University of Guelph, Guelph, Ontario, Canada.No affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22972179

Citation

Burgos, S A., et al. "Energy Depletion of Bovine Mammary Epithelial Cells Activates AMPK and Suppresses Protein Synthesis Through Inhibition of mTORC1 Signaling." Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, vol. 45, no. 3, 2013, pp. 183-9.
Burgos SA, Kim JJ, Dai M, et al. Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling. Horm Metab Res. 2013;45(3):183-9.
Burgos, S. A., Kim, J. J., Dai, M., & Cant, J. P. (2013). Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling. Hormone and Metabolic Research = Hormon- Und Stoffwechselforschung = Hormones Et Metabolisme, 45(3), 183-9. https://doi.org/10.1055/s-0032-1323742
Burgos SA, et al. Energy Depletion of Bovine Mammary Epithelial Cells Activates AMPK and Suppresses Protein Synthesis Through Inhibition of mTORC1 Signaling. Horm Metab Res. 2013;45(3):183-9. PubMed PMID: 22972179.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Energy depletion of bovine mammary epithelial cells activates AMPK and suppresses protein synthesis through inhibition of mTORC1 signaling. AU - Burgos,S A, AU - Kim,J J M, AU - Dai,M, AU - Cant,J P, Y1 - 2012/09/12/ PY - 2012/9/14/entrez PY - 2012/9/14/pubmed PY - 2013/9/27/medline SP - 183 EP - 9 JF - Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme JO - Horm Metab Res VL - 45 IS - 3 N2 - The molecular mechanisms by which cellular energy status regulates global protein synthesis in mammary epithelial cells have not been characterized. The objective of this study was to examine the effect of AMP-activated protein kinase (AMPK) activation by 2-deoxyglucose on protein synthesis and the mammalian target of rapamycin complex 1 (mTORC1) signaling pathway in bovine mammary epithelial cells. Phosphorylation of AMPK at Thr172 increased by 1.4-fold within 5 min, and remained elevated throughout a 30-min time course, in response to 2-deoxyglucose. Global rates of protein synthesis declined by 78% of control values. The decline in protein synthesis was associated with repression of mTORC1 signaling, as indicated by reduced phosphorylation of ribosomal protein S6 kinase 1 and eIF4E binding protein-1 (4E-BP1). Phosphorylation of ER-stress marker eIF2α was also increased but only at 30 min of 2-deoxyglucose exposure. 2-Deoxyglucose increased phosphorylation of tuberous sclerosis complex 2 (TSC2) on AMPK consensus sites but did not change the amount of TSC1 bound to TSC2. Activation of AMPK did not result in changes in the amount of raptor bound to mTOR. The inhibitory effects of AMPK activation on mTORC1 signaling were associated with a marked increase in Ser792 phosphorylation on raptor. Collectively, the results suggest that activation of AMPK represses global protein synthesis in mammary epithelial cells through inhibition of mTORC1 signaling. SN - 1439-4286 UR - https://www.unboundmedicine.com/medline/citation/22972179/Energy_depletion_of_bovine_mammary_epithelial_cells_activates_AMPK_and_suppresses_protein_synthesis_through_inhibition_of_mTORC1_signaling_ DB - PRIME DP - Unbound Medicine ER -