2021 Fiscal Year Final Research Report
Evaluation of recovery from hypoxic tissue damage in perioperative management
| Project/Area Number |
19K09344
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 55050:Anesthesiology-related
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| Research Institution | Yamagata University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
後藤 薫 山形大学, 医学部, 教授 (30234975)
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 細胞内情報伝達機構 / ジアシルグセロールキナーゼ / 低酸素応答 / エネルギーセンサー / AMPK / ATP |
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| Outline of Final Research Achievements |
In this study, we examined the functional implications of zeta type diacylglycerol kinase (DGKζ), a family of second messenger DG-metabolizing enzyme, after 1% hypoxic insults. Of hypoxia-responsive molecules, induction of hypoxia-inducible transcription factor HIF1alpha was attenuated. In addition, NAD-dependent deacetylase SIRT1 and NAD were also downregulated, suggesting that energy saving mechanism is not working. On the other hand, energy sensor AMPK was activated (increased phosphorylation) by upstream kinase TAK1. Since ATP level was increased by 1.2-fold after hypoxia, activation mechanism of energy sensor AMPK was dysregulated in DGKζ-KO cells. These results suggest that DGKζ deficiency results in suppressed prosurvival response via HIF1alpha and SIRT1 together with dysregulation of energy sensing system via AMPK.
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| Free Research Field |
麻酔科学
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| Academic Significance and Societal Importance of the Research Achievements |
損傷を受けた脳や臓器の生体応答は、急性期離脱後の回復を大きく左右すると考えられ、その評価は重要である。生体細胞を解析対象とした生体応答の評価法を確立することができれば、周術期管理に非常に有用と思われる。本研究では、臓器損傷に対する生体応答を、血管破綻による血流障害によって生じる「低酸素に対する生体応答」として捉え、種々の細胞・動物モデルを用いてその評価法を検討した。これらの研究結果は、将来的に臨床現場における生体侵襲応答評価法を確立するのに役立つものと考えられる。
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