Up regulation of autophagy in Hsp60 mutant heart is an adaptive response to increased oxidative stress and causes cardiomyopathy
| Project/Area Number |
25670397
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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 |
Cardiovascular medicine
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| Research Institution | Keio University |
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Principal Investigator |
Makino Shinji 慶應義塾大学, 医学部, 准教授 (20306707)
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| Project Period (FY) |
2013-04-01 – 2016-03-31
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| Project Status |
Completed (Fiscal Year 2015)
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| Budget Amount *help |
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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| Keywords | ゼブラフィッシュ変異体 / 拡張型心筋症 / 突然死 / 房室ブロック / 家族性心筋症 / 熱ショックタンパク / 心筋症 |
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| Outline of Final Research Achievements |
This study is aimed to determine if hsp60 dysfunction leads to cardiomyopathy. We have developed a zebrafish mutant, nbl, which has a missense mutation in hsp60, leading to the loss of function.WT embryos showed higher survival rate (81%), compared to 65% in case of nbl homozygous mutant, when subjected to 33°C. Surprisingly, 92% of nbl mutants showed a pericardial edema. Also, nbl homozygous mutants showed the sudden death around 8 months post fertilization (mpf). In 8 mpf, nbl mutants showed dilated heart and high ROS expression. mRNA expression pattern of atg5, atg3 and gabarap were found to very high in nbl homozygous compared to WT. Further, analysis of genetically unrelated patients with familial DCM, who had no mutations in the known DCM-causing genes, identified an hsp60 mutation in one DCM family in which two of four mutation prone individuals died suddenly. Over expression of nbl type or DCM patient-type mutation in Hsp60 increases autophagosomes.
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Report
(4 results)
Research Products
(27 results)
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[Journal Article] ET-1 induces myofibrillar disarray and contractile vector in hypertrophic cardiomyopathy-iPS cell-derived cardiomyocytes2014
Author(s)
Tanaka A, Yuasa S, Mearini G, Egashira T, Seki T, Kodaira M, Kusumoto D, Kuroda Y, Okata S, Suzuki T, Arimura T, Makino S, Kimura K, Kimura A, Furukawa T, Carrier L, Nobe K, Fukuda K
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Journal Title
J Am Heart Assoc
Volume: 3
Issue: 6
Pages: 1-25
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Presentation] Versican Facilitates the Differentiation and Migration of Endothelial Progenitor Cells in Yolk Sac for Vasculogenesis2013
Author(s)
Nishant Mittal, Sung Han Yun, Hirokazu Enomoto, Atsusi Kawakami, Akira Kudo, Misato Fujita, Atsushi Shimizu,Yoshihiko Saito, Osamu Nakagawa,Shinji Makino, Keiichi Fukuda
Organizer
American Heart Association’s Scientific Sessions
Place of Presentation
Dallas, USA
Related Report
