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
Document Type
Article
Publication Date
7-26-2011
Abstract
Bacground-: 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. © 2011 American Heart Association, Inc.
Identifier
79961031623 (Scopus)
Publication Title
Circulation
External Full Text Location
https://doi.org/10.1161/CIRCULATIONAHA.110.013847
e-ISSN
15244539
ISSN
00097322
PubMed ID
21747053
First Page
406
Last Page
415
Issue
4
Volume
124
Grant
R01HL106511
Fund Ref
National Heart, Lung, and Blood Institute
Recommended Citation
Qiu, Hongyu; Lizano, Paulo; Laure, Lydie; Sui, Xiangzhen; Rashed, Eman; Park, Ji Yeon; Hong, Chull; Gao, Shumin; Holle, Eric; Morin, Didier; Dhar, Sunil K.; Wagner, Thomas; Berdeaux, Alain; Tian, Bin; Vatner, Stephen F.; and Depre, Christophe, "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" (2011). Faculty Publications. 11256.
https://digitalcommons.njit.edu/fac_pubs/11256
