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  The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the antioxidant response

Kruger, A., Gruning, N. M., Wamelink, M. M., Kerick, M., Kirpy, A., Parkhomchuk, D., et al. (2011). The pentose phosphate pathway is a metabolic redox sensor and regulates transcription during the antioxidant response. Antioxidants & Redox Signaling, 15(2), 311-24. Retrieved from http://www.ncbi.nlm.nih.gov/pubmed/21348809 http://online.liebertpub.com/doi/pdfplus/10.1089/ars.2010.3797.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-78FA-D Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0010-78FB-B
Genre: Journal Article

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Kruger, A., Author
Gruning, N. M., Author
Wamelink, M. M., Author
Kerick, M.1, Author              
Kirpy, A.2, Author              
Parkhomchuk, D.2, Author              
Bluemlein, K.2, Author              
Schweiger, M. R.1, Author              
Soldatov, A.3, Author              
Lehrach, H.2, Author              
Jakobs, C., Author
Ralser, M.2, Author              
Affiliations:
1Cancer Genomics (Michal-Ruth Schweiger), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479649              
2Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433550              
3Technology Development(Alexey Soldatov), Dept. of Vertebrate Genomics (Head: Hans Lehrach), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479657              

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Free keywords: Antioxidants/*metabolism; Electron Transport; Gene Expression Profiling; *Gene Expression Regulation; Glycolysis; Mutation; NADP/metabolism; Oxidation-Reduction; *Pentose Phosphate Pathway; *Transcription, Genetic
 Abstract: AIMS: A shift in primary carbon metabolism is the fastest response to oxidative stress. Induced within seconds, it precedes transcriptional regulation, and produces reducing equivalents in form of NADPH within the pentose phosphate pathway (PPP). RESULTS: Here, we provide evidence for a regulatory signaling function of this metabolic transition in yeast. Several PPP-deficiencies caused abnormal accumulation of intermediate metabolites during the stress response. These PPP-deficient strains had strong growth deficits on media containing oxidants, but we observed that part of their oxidant-phenotypes were not attributable to the production of NADPH equivalents. This pointed to a second, yet unknown role of the PPP in the antioxidant response. Comparing transcriptome profiles obtained by RNA sequencing, we found gene expression profiles that resembled oxidative conditions when PPP activity was increased. Vice versa, deletion of PPP enzymes disturbed and delayed mRNA and protein expression during the antioxidant response. INNOVATION: Thus, the transient activation of the PPP is a metabolic signal required for balancing and timing gene expression upon an oxidative burst. CONCLUSION: Consequently, dynamic rearrangements in central carbon metabolism seem to be of major importance for eukaryotic redox sensing, and represent a novel class of dynamic gene expression regulators.

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 Dates: 2011
 Publication Status: Published in print
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Title: Antioxidants & Redox Signaling
Source Genre: Journal
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Pages: - Volume / Issue: 15 (2) Sequence Number: - Start / End Page: 311 - 24 Identifier: ISSN: 1557-7716 (Electronic) 1523-0864 (Linking)