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  Hepatocellular apoptosis in mice is associated with early upregulation of mitochondrial glucose metabolism

Gottschalk, S., Zwingmann, C., Raymond, V.-A., Hohnholt, M., Chan, T., & Bilodeau, M. (2012). Hepatocellular apoptosis in mice is associated with early upregulation of mitochondrial glucose metabolism. Apoptosis, 17(2), 143-153. doi:10.1007/s10495-011-0669-y.

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Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0013-B822-9 Version Permalink: http://hdl.handle.net/21.11116/0000-0001-89C1-A
Genre: Journal Article

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Gottschalk, S1, 2, Author              
Zwingmann, C, Author
Raymond, V-A, Author
Hohnholt, MC, Author
Chan, TS, Author
Bilodeau, M, Author
Affiliations:
1Department High-Field Magnetic Resonance, Max Planck Institute for Biological Cybernetics, Max Planck Society, ou_1497796              
2Max Planck Institute for Biological Cybernetics, Max Planck Society, Spemannstrasse 38, 72076 Tübingen, DE, ou_1497794              

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 Abstract: Hepatocyte death due to apoptosis is a hallmark of almost every liver disease. Manipulation of cell death regulatory steps during the apoptotic process is therefore an obvious goal of biomedical research. To clarify whether metabolic changes occur prior to the characteristic apoptotic events, we used ex vivo multinuclear NMR-spectroscopy to study metabolic pathways of [U-13C]glucose in mouse liver during Fas-induced apoptosis. We addressed whether these changes could be associated with protection against apoptosis afforded by Epidermal Growth Factor (EGF). Our results show that serum alanine and aspartate aminotransferase levels, caspase-3 activity, BID cleavage and changes in cellular energy stores were not observed before 3 h following anti-Fas injection. However, as early as 45 min after anti-Fas treatment, we observed upregulation of carbon entry (i.e. flux) from glucose into the Krebs-cycle via pyruvate dehydrogenase (PDH) and pyruvate carboxylase (PC) (up to 139 and 123 of controls, respectively, P < 0.001). This was associated with increased glutathione synthesis. EGF treatment significantly attenuated Fas-induced apoptosis, liver injury and the late decrease in energy stores, as well as the early fluxes through PDH and PC which were comparable to untreated controls. Using ex vivo multinuclear NMR-spectroscopic analysis, we have shown that Fas receptor activation in mouse liver time-dependently affects specific metabolic pathways of glucose. These early upregulations in glucose metabolic pathways occur prior to any visible signs of apoptosis and may have the potential to contribute to the initiation of apoptosis by maintaining mitochondrial energy production and cellular glutathione stores.

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 Dates: 2012-02
 Publication Status: Published in print
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 Rev. Type: -
 Identifiers: DOI: 10.1007/s10495-011-0669-y
BibTex Citekey: GottschalkZRHCB2011
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Title: Apoptosis
Source Genre: Journal
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Publ. Info: Norwell, MA : Kluwer Academic Publishers
Pages: - Volume / Issue: 17 (2) Sequence Number: - Start / End Page: 143 - 153 Identifier: ISSN: 1360-8185
CoNE: https://pure.mpg.de/cone/journals/resource/954925619145