| Hepatocellular apoptosis in mice is associated with early upregulation of mitochondrial glucose metabolism. | |
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MedLine Citation:
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PMID: 22109881 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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-(13)C]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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Authors:
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Sven Gottschalk; Claudia Zwingmann; Valérie-Ann Raymond; Michaela C Hohnholt; Tom S Chan; Marc Bilodeau |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-23 |
Journal Detail:
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Title: Apoptosis : an international journal on programmed cell death Volume: - ISSN: 1573-675X ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9712129 Medline TA: Apoptosis Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Centre de recherche, Centre hospitalier du l'Université de Montréal, Hôpital Saint-Luc, 264, boul. René-Lévesque est, Montréal, QC, H2X 1P1, Canada, gottschalk.sven@gmail.com. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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