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著作: Morishima Masaki/[堀川 一樹]/Funaki Makoto/Cardiomyocytes cultured on mechanically compliant substrates, but not on conventional culture devices, exhibit prominent mitochondrial dysfunction due to reactive oxygen species and insulin resistance under high glucose./[PLoS ONE]

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EID
356639
EOID
958113
Map
0
LastModified
2019年8月21日(水) 14:14:43
Operator
大家 隆弘
Avail
TRUE
Censor
0
Owner
堀川 一樹
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種別 必須
言語 必須 英語
招待 推奨
審査 推奨
カテゴリ 推奨
共著種別 推奨
学究種別 推奨
組織 推奨
著者 必須
  1. (英) Morishima Masaki
    役割 任意
    貢献度 任意
    学籍番号 推奨
  2. 堀川 一樹([徳島大学.先端研究推進センター.バイオイメージング研究部門])
    役割 任意
    貢献度 任意
    学籍番号 推奨
  3. (英) Funaki Makoto
    役割 任意
    貢献度 任意
    学籍番号 推奨
題名 必須

(英) Cardiomyocytes cultured on mechanically compliant substrates, but not on conventional culture devices, exhibit prominent mitochondrial dysfunction due to reactive oxygen species and insulin resistance under high glucose.

副題 任意
要約 任意

(英) Diabetes causes cardiac dysfunction, and understanding of its mechanism is still incomplete. One reason could be limitations in modeling disease conditions by current in vitro cardiomyocyte culture. Emerging evidence suggests that the mechanical properties of the microenvironment affect cardiomyocyte function. Nevertheless, the impact of high glucose on cardiomyocytes cultured on substrates whose stiffness matches that of the heart (approximately 15 kPa) is untested. To test the hypothesis that cardiomyocytes cultured in microenvironments that mimic the mechanical properties of those for cardiomyocytes in vivo may reproduce the pathophysiology characteristics of diabetic cardiomyocytes ex vivo, such as the morphological appearance, ROS accumulation, mitochondrial dysfunction, apoptosis and insulin-stimulated glucose uptake. Isolated neonatal rat cardiomyocytes were seeded on 15 kPa polyacrylamide (PAA) gels, whose stiffness mimics that of heart tissues, or on glass coverslips, which represent conventional culture devices but are unphysiologically stiff. Cells were then cultured at 5 mM glucose, corresponding to the normal blood glucose level, or at high glucose levels (10 to 25 mM). Cytoskeletal disorganization, ROS accumulation, attenuated mitochondrial membrane potential and attenuated ATP level caused by high glucose and their reversal by a ROS scavenger were prominent in cells on gels, but not in cells on coverslips. The lack of response to ROS scavenging could be attributable to enhanced apoptosis in cells on glass, shown by enhanced DNA fragmentation and higher caspase 3/7 activity in cells on glass coverslips. High-glucose treatment also downregulated GLUT4 expression and attenuated insulin-stimulated glucose uptake only in cells on 15 kPa gels. Our data suggest that a mechanically compliant microenvironment increases the susceptibility of primary cardiomyocytes to elevated glucose levels, which enables these cells to serve as an innovative model for diabetic heart research.

キーワード 推奨
  1. (英) Animals
  2. (英) Animals, Newborn
  3. (英) Biomechanical Phenomena
  4. (英) Cell Culture Techniques
  5. (英) Cells, Cultured
  6. (英) Culture Media
  7. (英) Cytoskeleton
  8. (英) Elasticity
  9. (英) Glucose
  10. (英) Heart Ventricles
  11. (英) Insulin Resistance
  12. (英) Mitochondria
  13. (英) Myocytes, Cardiac
  14. (英) Rats, Wistar
  15. (英) Reactive Oxygen Species
発行所 推奨
誌名 必須 PLoS ONE(Public Library of Science)
(eISSN: 1932-6203)
ISSN 任意 1932-6203
ISSN: 1932-6203 (eISSN: 1932-6203)
Title: PloS one
Title(ISO): PLoS One
Publisher: PLOS
 (NLM Catalog  (Scopus  (CrossRef (Scopus information is found. [need login])
必須 13
必須 8
必須 e0201891 e0201891
都市 任意
年月日 必須 2018年 8月 23日
URL 任意
DOI 任意 10.1371/journal.pone.0201891    (→Scopusで検索)
PMID 任意 30138395    (→Scopusで検索)
NAID 任意
WOS 任意
Scopus 任意
評価値 任意
被引用数 任意
指導教員 推奨
備考 任意
  1. (英) Article.ELocationID: 10.1371/journal.pone.0201891

  2. (英) Article.PublicationTypeList.PublicationType: Comparative Study

  3. (英) Article.PublicationTypeList.PublicationType: Journal Article

  4. (英) Article.PublicationTypeList.PublicationType: Research Support, Non-U.S. Gov't

  5. (英) CoiStatement: I have read the journal's policy and the authors of this manuscript have the following competing interests: M.F. is a board member of Mechanogenic Inc. This does not alter our adherence to PLOS ONE policies on sharing data and materials. No other potential conflict of interest relevant to this article is reported.