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Does excessive cysteine intake exacerbate the atherosclerosis?

Research Project

Project/Area Number 18K17977
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 59040:Nutrition science and health science-related
Research InstitutionJuntendo University

Principal Investigator

Hashimoto Ryota  順天堂大学, 医学部, 准教授 (60433786)

Project Period (FY) 2018-04-01 – 2022-03-31
Project Status Completed (Fiscal Year 2021)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2019: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsシステイン / シスチン / マクロファージ / 酸化LDL / 動脈硬化
Outline of Final Research Achievements

Phagocytosis of oxidized LDL by macrophages is an important process in the development of atherosclerosis. Cystine, a metabolite of cysteine, enhanced the uptake of oxidized LDL by macrophages (in vitro). Macrophages treated with reagents inducing ER stress showed reduced uptake of oxidized LDL, whereas this was not the case in the presence of cystine (in vitro). These results suggest that macrophages that have taken up oxidized LDL might have reduced the capacity for oxidized LDL uptake due to ER stress, whereas macrophages that have taken up oxidized LDL might maintain their ability to uptake oxidized LDL in the presence of cystine. In vivo, however, no difference in uptake of oxidized LDL was observed in macrophages from cystine-fed mice. We would like to examine the relationship between ER stress and cystine in vivo in the near future.

Academic Significance and Societal Importance of the Research Achievements

アミノ酸の一種であるシステインは、色素沈着や二日酔いの改善などのサプリメントとして広く利用されている。In vitroの結果からは、システインの代謝物であるシスチンが酸化LDLによるERストレスを抑えることでマクロファージの酸化LDL取込みを促進する可能性が示唆された。今回、in vivoの結果からはシスチンが動脈硬化を増悪させるデータは得られなかった。しかし、ERストレスが生じている環境下では、シスチンが動脈硬化を増悪させる可能性は否定できない。また、過剰なシステイン摂取が糖尿病を悪化させる可能性が報告されていることを考慮すると、適度なサプリメント摂取が望ましいと考える。

Report

(5 results)
  • 2021 Annual Research Report   Final Research Report ( PDF )
  • 2020 Research-status Report
  • 2019 Research-status Report
  • 2018 Research-status Report
  • Research Products

    (8 results)

All 2022 2020 2018

All Journal Article (5 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 5 results,  Open Access: 1 results) Presentation (3 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] G6PD is a critical enabler of hypoxia-induced accumulation of macrophages and platelets in mice lungs and contributor to lung inflammation2022

    • Author(s)
      Hashimoto Ryota、Gupte Sachin A.
    • Journal Title

      Vascular Pharmacology

      Volume: 144 Pages: 106976-106976

    • DOI

      10.1016/j.vph.2022.106976

    • Related Report
      2021 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] JAK-STAT-dependent regulation of scavenger receptors in LPS-activated murine macrophages2020

    • Author(s)
      Hashimoto Ryota、Kakigi Ryo、Miyamoto Yuki、Nakamura Kyoko、Itoh Seigo、Daida Hiroyuki、Okada Takao、Katoh Youichi
    • Journal Title

      European Journal of Pharmacology

      Volume: 871 Pages: 172940-172940

    • DOI

      10.1016/j.ejphar.2020.172940

    • Related Report
      2020 Research-status Report 2019 Research-status Report
    • Peer Reviewed
  • [Journal Article] Hypoxic activation of glucose-6-phosphate dehydrogenase controls the expression of genes involved in the pathogenesis of pulmonary hypertension through the regulation of DNA methylation2020

    • Author(s)
      Joshi Sachindra Raj、Kitagawa Atsushi、Jacob Christina、Hashimoto Ryota、Dhagia Vidhi、Ramesh Amrit、Zheng Connie、Zhang Hui、Jordan Allan、Waddell Ian、Leopold Jane、Hu Cheng-Jun、McMurtry Ivan F.、D’Alessandro Angelo、Stenmark Kurt R.、Gupte Sachin A.
    • Journal Title

      American Journal of Physiology-Lung Cellular and Molecular Physiology

      Volume: 318 Issue: 4 Pages: L773-L786

    • DOI

      10.1152/ajplung.00001.2020

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Pluripotent hematopoietic stem cells augment α-adrenergic receptor-mediated contraction of pulmonary artery and contribute to the pathogenesis of pulmonary hypertension2020

    • Author(s)
      Hashimoto Ryota、Lanier Gregg M.、Dhagia Vidhi、Joshi Sachindra R.、Jordan Allan、Waddell Ian、Tuder Rubin、Stenmark Kurt R.、Wolin Michael S.、McMurtry Ivan F.、Gupte Sachin A.
    • Journal Title

      American Journal of Physiology-Lung Cellular and Molecular Physiology

      Volume: 318 Issue: 2 Pages: L386-L401

    • DOI

      10.1152/ajplung.00327.2019

    • Related Report
      2020 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] A simple method to increase the proportion of bonemarrow-derived macrophages positive for M-CSFR using the reducing agent dithiothreitol (DTT)2018

    • Author(s)
      Hashimoto-R, Daida-H, Okada-T, Katoh-Y
    • Journal Title

      Methods X

      Volume: 5 Pages: 1540-1548

    • DOI

      10.1016/j.mex.2018.11.014

    • Related Report
      2018 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] G6PD and CYP450 Enzyme Regulate Hematopoietic Stem Cell Biology: Implication to Pulmonary Artery Remodeling in Pulmonary Hypertension2018

    • Author(s)
      Ryota Hashimoto, Sachindra Raj Joshi, Houli Jiang, Jorge H. Capdevila, Michal Laniado Schwartzman, Sachin A. Gupte
    • Organizer
      American Heart Association’s Scientific Sessions 2018
    • Related Report
      2018 Research-status Report
    • Int'l Joint Research
  • [Presentation] Glucocorticoid decreases uptake of Ac-LDL through suppression of JAK-STAT pathway in macrophages2018

    • Author(s)
      Ryota Hashimoto, Ryo Kakigi, Kyoko Nakamura, Yuki Miyamoto, Hiroyuki Daida, Takao Okada, Youichi Katoh
    • Organizer
      第2回日本循環器学会基礎研究フォーラム
    • Related Report
      2018 Research-status Report
  • [Presentation] Glucocorticoid decreases uptake of Ac-LDL through suppression of JAK-STATpathway in bone marrow-derived macrophages2018

    • Author(s)
      Ryota Hashimoto, Yuki Miyamoto, Ryo Kakigi, Kyoko Nakamura, Hiroyuki Daida, Takao Okada, Youichi Katoh
    • Organizer
      第83回日本循環器学会学術集会
    • Related Report
      2018 Research-status Report

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Published: 2018-04-23   Modified: 2023-01-30  

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