2016 Fiscal Year Final Research Report
Novel methods to regulate hepatic graft by extracorporial perfusion : Chaperoen mediated mechanisms
| Project/Area Number |
26670572
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Multi-year Fund |
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| Research Field |
General surgery
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| Research Institution | Hokkaido University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 移植・再生医療 / 外科 / 発現制御 / 臓器灌流 |
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| Outline of Final Research Achievements |
The role of 14-3-3 zeta on the cellular injury and energy production during and after hypothermic storage with or without oxygen, using mouse hepatocytes derived cell line (AML12). 14-3-3 zeta overexpression was introduced by gene delivery or some small molecule. After confirmation of 14-3-3 zeta protein level, cells were subjected to hypothermic oxygenate condition mimicking the cellular environment during organ perfusion. Combination of 14-3-3 zeta inducing molecule and hydrogen sulfide strengthen the mitochondrial functions related to oxidative phosphorylation, drug (MTT) metabolism, and antioxidant ability, due to the prevention of protein dephosphorylation (14-3-3) and stimulation of ARE-binding transcription factors (NaHS). These results revealed novel strategy to pre-condition the marginal graft not by gene delivery but by transcriptional and post-translational regulations.
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| Free Research Field |
移植外科
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