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Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy

ABSTRACT: This SuperSeries is composed of the following subset Series: GSE35701: CP001: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy GSE35703: CP003: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy Refer to individual Series

ORGANISM(S): Mus musculus

SUBMITTER: Marian Groot Koerkamp

PROVIDER: E-GEOD-35705 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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CP001: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy

Project description:The PI3K-PKB/c-akt-FOXO signalling network provides a major intracellular hub for regulation of cell proliferation, survival and stress resistance1. Here we report a novel function for FOXO transcription factors in regulating autophagy through modulation of intracellular glutamine levels. To identify novel transcriptional targets of this module we performed an unbiased microarray analysis after conditional activation of the key components PI3K, PKB, FOXO3 and FOXO4. Utilising this global pathway approach we identified glutamine synthetase (GS) as being transcriptionally regulated by PI3K-PKB-FOXO signalling. FOXO-mediated increase in GS expression specifically induced glutamine production independently of cell type, and this was evolutionary conserved. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes, which was dependent on GS activity. Increased GS activity resulted in increased autophagosome turnover as measured by LC3 lipidation, p62 degradation, and confocal imaging of LC3, p62, WIPI-1, ULK2 and Atg12. Inhibition of FOXO3-mediated autophagy resulted in increased apoptosis, suggesting that the induction of autophagy by FOXO3-mediated upregulation of GS is important for cellular survival. These findings reveal a novel signalling network that can directly modulate autophagy through regulation of glutamine metabolism. conditional activation of pkb and pi3k were followed in a timeseries. Each timepoint consists of 4 independent replicates, labeled with either cy3 or cy5 and put on array against time0.

2012-07-21 | E-GEOD-35701 | biostudies-arrayexpress

CP003: Modulation of glutamine metabolism by the PI3K-PKB/c-akt-FOXO network regulates autophagy

Project description:The PI3K-PKB/c-akt-FOXO signalling network provides a major intracellular hub for regulation of cell proliferation, survival and stress resistance1. Here we report a novel function for FOXO transcription factors in regulating autophagy through modulation of intracellular glutamine levels. To identify novel transcriptional targets of this module we performed an unbiased microarray analysis after conditional activation of the key components PI3K, PKB, FOXO3 and FOXO4. Utilising this global pathway approach we identified glutamine synthetase (GS) as being transcriptionally regulated by PI3K-PKB-FOXO signalling. FOXO-mediated increase in GS expression specifically induced glutamine production independently of cell type, and this was evolutionary conserved. FOXO activation resulted in mTOR inhibition by preventing the translocation of mTOR to lysosomal membranes, which was dependent on GS activity. Increased GS activity resulted in increased autophagosome turnover as measured by LC3 lipidation, p62 degradation, and confocal imaging of LC3, p62, WIPI-1, ULK2 and Atg12. Inhibition of FOXO3-mediated autophagy resulted in increased apoptosis, suggesting that the induction of autophagy by FOXO3-mediated upregulation of GS is important for cellular survival. These findings reveal a novel signalling network that can directly modulate autophagy through regulation of glutamine metabolism. conditional activation of foxo3 and foxo4 were followed in a timeseries. Each timepoint consists of 4 independent replicates, labeled with either cy3 or cy5 and put on array against time0 as reference.

2012-07-21 | E-GEOD-35703 | biostudies-arrayexpress

Transcription profiling of heptatocytes from mice given a high-copper diet

Project description:In order to study the physiological consequences of a high-copper diet on hepatic gene expression, 6 mM CuCl2 was added to the drinking water for a period of 1 month. After this period, livers of seven control mice and eight copper-treated mice were isolated and were subjected to microarray analysis and copper measurements. The hepatic gene expression profile of copper-treated mice was compared to non-treated mice using a pooled reference.

2007-06-01 | E-MEXP-745 | biostudies-arrayexpress

Transcription profiling of human hepatocytes in response to copper overload at nine time points

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2007-06-01 | E-MEXP-753 | biostudies-arrayexpress

Transcription profiling of six pairs of affected and non-affected male F2 mice selected on the basis of their motor activity levels

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2006-12-31 | E-UMCU-22 | biostudies-arrayexpress

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2006-09-01 | E-MEXP-832 | biostudies-arrayexpress

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2009-08-14 | E-TABM-754 | biostudies-arrayexpress

Transcription profiling of matching human primary head and neck squamous cell carcinomas and cervical lymph node metastases.

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2006-10-23 | E-TABM-114 | biostudies-arrayexpress

Transcription profiling of honey bee queens treated with carbon dioxide and physical manipulation vs virgin controls

Project description:Mating is a complex process that causes many behavioral and physiological changes, but the factors triggering these changes and the underlying molecular processes are not well characterized. Honey bee queens provide a convenient system for dissecting these factors (e.g., physical manipulation, insemination volume, insemination substance) via instrumental insemination. We examined the effects of carbon dioxide (CO2), a commonly used anesthetic in instrumental insemination that causes changes similar to those observed after mating, and physical manipulation, which presumably mimics the act of copulation, on the brain transcriptional changes in honey bee queens. We found significant gene overlap between our study and previous mating studies in honey bee queens and Drosophila. This suggests that molecular pathways regulating the mating process are conserved across different mating regimes of honey bees as well as across insect orders.

2011-01-30 | E-MEXP-2646 | biostudies-arrayexpress

Transcription profiling of adult male whole MutaMouse lung with its immortalized 100% confluent epithelial lung cell line counterpart Codelink Bioarrays

Project description:Biological comparison of gene expression profiles of adult male whole MutaMouse lung with its immortalized 100% confluent epithelial lung cell line counterpart. White, P.A.,et al. 2003. Development and characterization of an epithelial cell line from MutaMouse lung. Environ Mol Mutagen 42,3 pgs 166-184

2004-07-01 | E-MEXP-109 | biostudies-arrayexpress

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