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Examination of the endoplasmic reticulum stress control for the arrhythmia disease.

Research Project

Project/Area Number 16K10078
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pediatrics
Research InstitutionTokyo Women's Medical University

Principal Investigator

FURUTANI MICHIKO  東京女子医科大学, 医学部, 研究生 (40398805)

Co-Investigator(Kenkyū-buntansha) 中西 敏雄  公益財団法人日本心臓血圧研究振興会(臨床研究施設・研究部門), 国際分子細胞免疫研究センター, 施設長 (90120013)
Project Period (FY) 2016-04-01 – 2019-03-31
Project Status Completed (Fiscal Year 2018)
Budget Amount *help
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2018: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2016: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
KeywordsNav1.5チャネル / 小胞体ストレス / QT延長症候群 / ホルモン / 不整脈疾患
Outline of Final Research Achievements

Recently, it has been focusing " endoplasmic reticulum stress", accumulation of immature and unfolding protein in the endoplasmic reticulum leads injure of cells and could be cause of many diseases. In this study, we examined factors that cause endoplasmic reticulum stress for the cardiac muscle channel, which is the protein responsible for the long QT syndrome. We established the stable cell line expressing R1623Q of the SCN5A (Nav1.5) mutant protein which was a myocardial Na+ channel gene. Using each stable cell line, we performed patch-clamp recordings in before and after adding estrogen, progesterone, fexofenadine and resveratrol, and confirm the change of the expression electric current. We found that only in mutant human Nav1.5 channel following the administration of the progesterone, the peak value tends to suppress the expression electric current.

Academic Significance and Societal Importance of the Research Achievements

不整脈疾患の多くが、心筋のチャネル蛋白の異常により生じている。特に、QT延長症候群の約10%は心停止が初発症状でもあるという点からも、予知と予防が極めて重要である。不整脈疾患における小胞体ストレスに関する研究は、国内外とも少ない。不整脈疾患における小胞体ストレスの制御が可能であれば、新たな予防法、治療法の開発などにつながる。本研究の成果は、無症候性の不整脈疾患発症の予防、治療を行う上での一つの指標となることが期待される。今後、今回得られた結果がいかに小胞体ストレスにより引き起こされたか等の詳細な検討を行い、不整脈疾患の新しい発症予防法や治療法の創出につなげることが必要である。

Report

(4 results)
  • 2018 Annual Research Report   Final Research Report ( PDF )
  • 2017 Research-status Report
  • 2016 Research-status Report

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Published: 2016-04-21   Modified: 2020-03-30  

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