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
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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