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Evidence for a role of immunoproteasomes in regulating cardiac muscle mass in diabetic mice
Zu, Lingyun1,2; Bedja, Djahida3; Fox-Talbot, Karen4; Gabrielson, Kathleen L.3; Van Kaer, Luc5; Becker, Lewis C.1; Cai, Zheqing P.1
关键词Proteasome PTEN Cardiomyopathy Heart failure Hyperglycemia
刊名JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY
2010-07-01
DOI10.1016/j.yjmcc.2010.02.007
49期:1页:5-15
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Cardiac & Cardiovascular Systems ; Cell Biology
研究领域[WOS]Cardiovascular System & Cardiology ; Cell Biology
关键词[WOS]PRECONDITIONING-INDUCED CARDIOPROTECTION ; UBIQUITIN-PROTEASOME SYSTEM ; SKELETAL-MUSCLE ; HEART-FAILURE ; GENE-EXPRESSION ; UP-REGULATION ; S PROTEASOME ; IN-VIVO ; CARDIOMYOPATHY ; TRANSCRIPTION
英文摘要

The ubiquitin-proteasome system plays an important role in regulating muscle mass Inducible immunoproteasome subunits LMP-2 and LMP-7 are constitutively expressed in the heart, however, their regulation and functions are poorly understood We here investigated the hypothesis that immunoproteasomes regulate cardiac muscle mass in diabetic mice. Type 1 diabetes was induced in wildtype mice by streptozotocin After hyperglycemia developed, insulin and the proteasome inhibitor epoxomicin were used to treat diabetic mice for 6 weeks Isolated mouse hearts were perfused with control or high glucose solution Catalytic proteasome beta-subunits and proteolytic activities were analyzed in the heart by immunoblotting and fluorogenic peptide degradation assays, respectively. Insulin and epoxomicin blocked loss of heart weight and improved cardiac function in diabetic mice LMP-7 and its corresponding chymotryptic-like proteasome activity were increased in diabetic hearts and high glucose-treated hearts Myosin heavy chain protein was decreased in diabetic hearts, which was largely reversed by epoxomicin. High glucose decreased LMP-2 protein levels in perfused hearts In diabetic hearts, LMP-2 expression was downregulated whereas expression of the phosphatase and tensin homologue deleted on chromosome ten (PTEN) and the muscle atrophy F-box were upregulated Moreover, mice with muscle-specific knockout of PTEN gene demonstrated increased cardiac muscle mass, while mice with LMP-2 deficiency demonstrated PTEN accumulation, muscle mass loss, and contractile impairment in the heart. Therefore, we concluded that high glucose regulates immunoproteasome subunits and modifies proteasome activities in the heart, and that dysregulated immunoproteasome subunits may mediate loss of cardiac muscle mass in experimental diabetic mice (C) 2010 Elsevier Ltd All rights reserved

语种英语
WOS记录号WOS:000278750300002
项目编号P01-HL65608 ; HL88071
资助机构National Heart, Lung and Blood Institute, National Institutes of Health
引用统计
被引频次:24[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/58244
专题北京大学第三临床医学院_心血管内科
作者单位1.Johns Hopkins Univ, Sch Med, Dept Med, Div Cardiol, Baltimore, MD 21205 USA
2.Peking Univ, Hosp 3, Dept Cardiol, Beijing 100191, Peoples R China
3.Johns Hopkins Med Inst, Div Comparat Med, Baltimore, MD 21205 USA
4.Johns Hopkins Univ, Sch Med, Dept Pathol, Baltimore, MD 21205 USA
5.Vanderbilt Univ, Sch Med, Dept Microbiol & Immunol, Nashville, TN 37232 USA
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Zu, Lingyun,Bedja, Djahida,Fox-Talbot, Karen,et al. Evidence for a role of immunoproteasomes in regulating cardiac muscle mass in diabetic mice[J]. JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,2010,49(1):5-15.
APA Zu, Lingyun.,Bedja, Djahida.,Fox-Talbot, Karen.,Gabrielson, Kathleen L..,Van Kaer, Luc.,...&Cai, Zheqing P..(2010).Evidence for a role of immunoproteasomes in regulating cardiac muscle mass in diabetic mice.JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY,49(1),5-15.
MLA Zu, Lingyun,et al."Evidence for a role of immunoproteasomes in regulating cardiac muscle mass in diabetic mice".JOURNAL OF MOLECULAR AND CELLULAR CARDIOLOGY 49.1(2010):5-15.
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