H11 Kinase/Heat Shock Protein 22 Deletion Impairs Both Nuclear and Mitochondrial Functions of STAT3 and Accelerates the Transition Into Heart Failure on Cardiac Overload
Autor: | Chull Hong, Hongyu Qiu, Shumin Gao, Paulo Lizano, Eric Holle, Lydie Laure, Thomas E. Wagner, Eman Rashed, Alain Berdeaux, Bin Tian, Xiangzhen Sui, Christophe Depre, Sunil Dhar, Stephen F. Vatner, Didier Morin, Ji Yeon Park |
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Přispěvatelé: | Department of cell biology and molecular medicine, Cardiovascular Research Institute-University of Medicine and Dentistry-Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers)-Rutgers University System (Rutgers), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10, Department of biochemistry and molecular biology, Rutgers New Jersey Medical School (NJMS), Rutgers University System (Rutgers)-Rutgers University System (Rutgers)-Rutgers Biomedical and Health Sciences, Rutgers University System (Rutgers), Oncology Research Institute, Hospital System University Medical Center-Clemson University, Department of Mathematical Sciences, Institute of Technology-Center for Applied Mathematics and Statistics, Study supported by NIH grants HL 072863, HL 093415, HL033107, A6027211, HL069020 and AHA grant 0230017N |
Jazyk: | angličtina |
Rok vydání: | 2011 |
Předmět: |
Male
Overload Muscle Proteins Mitochondria Heart Oxidative Phosphorylation chemistry.chemical_compound Mice 0302 clinical medicine Myocyte Myocytes Cardiac STAT3 Cells Cultured Heat-Shock Proteins Mice Knockout 0303 health sciences biology STAT NF-kappa B Knockout mouse Collagen Signal transduction Cardiology and Cardiovascular Medicine STAT3 Transcription Factor medicine.medical_specialty Cardiomegaly Heart failure Article 03 medical and health sciences Physiology (medical) Internal medicine Heat shock protein medicine Animals HSP20 Heat-Shock Proteins [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology Transcription factor 030304 developmental biology Pressure overload Cell Nucleus Heat shock proteins Interleukin-6 Gene Expression Profiling Tyrosine phosphorylation Rats Endocrinology chemistry biology.protein 030217 neurology & neurosurgery Gene Deletion Molecular Chaperones |
Zdroj: | Circulation Circulation, American Heart Association, 2011, 124 (4), pp.406-15. ⟨10.1161/CIRCULATIONAHA.110.013847⟩ |
ISSN: | 0009-7322 1524-4539 |
Popis: | Background— Cardiac overload, a major cause of heart failure, induces the expression of the heat shock protein H11 kinase/Hsp22 (Hsp22). Methods and Results— To determine the specific function of Hsp22 in that context, a knockout mouse model of Hsp22 deletion was generated. Although comparable to wild-type mice in basal conditions, knockout mice exposed to pressure overload developed less hypertrophy and showed ventricular dilation, impaired contractile function, increased myocyte length and accumulation of interstitial collagen, faster transition into heart failure, and increased mortality. Microarrays revealed that hearts from knockout mice failed to transactivate genes regulated by the transcription factor STAT3. Accordingly, nuclear STAT3 tyrosine phosphorylation was decreased in knockout mice. Silencing and overexpression experiments in isolated neonatal rat cardiomyocytes showed that Hsp22 activates STAT3 via production of interleukin-6 by the transcription factor nuclear factor-κB. In addition to its transcriptional function, STAT3 translocates to the mitochondria where it increases oxidative phosphorylation. Both mitochondrial STAT3 translocation and respiration were also significantly decreased in knockout mice. Conclusions— This study found that Hsp22 represents a previously undescribed activator of both nuclear and mitochondrial functions of STAT3, and its deletion in the context of pressure overload in vivo accelerates the transition into heart failure and increases mortality. |
Databáze: | OpenAIRE |
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