2013 Fiscal Year Final Research Report
Genetic analysis of the systemic damage response via caspase pathway to maintain homeostasis
| Project Area | Homeostatic inflammation: Molecular basis and dysregulation |
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| Project/Area Number |
21117006
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| Research Category |
Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)
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| Allocation Type | Single-year Grants |
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| Review Section |
Biological Sciences
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| Research Institution | The Institute of Physical and Chemical Research (2011-2013)
The University of Tokyo (2009-2010) |
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Principal Investigator |
KURANAGA Erina 独立行政法人理化学研究所, 発生・再生科学総合研究センター, チームリーダー (90376591)
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| Project Period (FY) |
2009-07-23 – 2014-03-31
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| Keywords | カスパーゼ / 非感染性炎症 / ショウジョウバエ / 内因性リガンド |
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| Research Abstract |
In this study, we focused on stress responses and metabolic alterations in the Drosophila apaf-1 (dpf-1) mutant, in which caspase activation and subsequent apoptosis are severely impaired. The dpf-1 mutant was found to be sensitive to injury- and starvation-stress. We show that dpf-1 mutant has defects in homeostatic gut cell renewal and that inhibiting caspase activity in fly enterocytes results in the production of systemic lethal factors after wounding. We then conducted metabolomic analyses of the hemolymph in dpf-1 mutants to investigate the physiological consequences of caspase inhibition. Several metabolites were found at higher levels in dpf-1 mutants than in wild type, which for at least one of the metabolites, was likely due to alteration of expression levels of putative metabolic enzymes in the fat body. Together, these results suggest caspase activity is required in the gut to regulate the systemic defense response in order to overcome stress in vivo.
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