H11 kinase is a novel mediator of myocardial hypertrophy in vivo
- PMID: 12456486
- DOI: 10.1161/01.res.0000044380.54893.4b
H11 kinase is a novel mediator of myocardial hypertrophy in vivo
Abstract
By subtractive hybridization, we found a significant increase in H11 kinase transcript in large mammalian models of both ischemia/reperfusion (stunning) and chronic pressure overload with hypertrophy. Because this gene has not been characterized in the heart, the goal of the present study was to determine the function of H11 kinase in cardiac tissue, both in vitro and in vivo. In isolated neonatal rat cardiac myocytes, adenoviral-mediated overexpression of H11 kinase resulted in a 37% increase in protein/DNA ratio, reflecting hypertrophy. A cardiac-specific transgene driven by the alphaMHC-promoter was generated, which resulted in an average 7-fold increase in H11 kinase protein expression. Transgenic hearts were characterized by a 30% increase of the heart weight/body weight ratio, by the reexpression of a fetal gene program, and by concentric hypertrophy with preserved contractile function at echocardiography. This phenotype was accompanied by a dose-dependent activation of Akt/PKB and p70(S6) kinase, whereas the MAP kinase pathway was unaffected. Thus, H11 kinase represents a novel mediator of cardiac cell growth and hypertrophy.
Similar articles
-
Activation of distinct signal transduction pathways in hypertrophied hearts by pressure and volume overload.Basic Res Cardiol. 2004 Sep;99(5):328-37. doi: 10.1007/s00395-004-0482-7. Epub 2004 Jul 21. Basic Res Cardiol. 2004. PMID: 15309410
-
Akt3 overexpression in the heart results in progression from adaptive to maladaptive hypertrophy.J Mol Cell Cardiol. 2005 Feb;38(2):375-85. doi: 10.1016/j.yjmcc.2004.12.002. Epub 2005 Jan 25. J Mol Cell Cardiol. 2005. PMID: 15698844
-
Phenotypic spectrum caused by transgenic overexpression of activated Akt in the heart.J Biol Chem. 2002 Jun 21;277(25):22896-901. doi: 10.1074/jbc.M200347200. Epub 2002 Apr 9. J Biol Chem. 2002. PMID: 11943770
-
Therapeutic potential of H11 kinase for the ischemic heart.Cardiovasc Drug Rev. 2007 Spring;25(1):14-29. doi: 10.1111/j.1527-3466.2007.00002.x. Cardiovasc Drug Rev. 2007. PMID: 17445085 Review.
-
Regulation of cell size and contractile function by AKT in cardiomyocytes.Ann N Y Acad Sci. 2004 May;1015:250-60. doi: 10.1196/annals.1302.021. Ann N Y Acad Sci. 2004. PMID: 15201165 Review.
Cited by
-
HSP22 suppresses diabetes-induced endothelial injury by inhibiting mitochondrial reactive oxygen species formation.Redox Biol. 2019 Feb;21:101095. doi: 10.1016/j.redox.2018.101095. Epub 2019 Jan 3. Redox Biol. 2019. PMID: 30640127 Free PMC article.
-
H11 has dose-dependent and dual hypertrophic and proapoptotic functions in cardiac myocytes.Biochem J. 2005 Jun 1;388(Pt 2):475-83. doi: 10.1042/BJ20041314. Biochem J. 2005. PMID: 15656793 Free PMC article.
-
The valosin-containing protein is a novel mediator of mitochondrial respiration and cell survival in the heart in vivo.Sci Rep. 2017 Apr 20;7:46324. doi: 10.1038/srep46324. Sci Rep. 2017. PMID: 28425440 Free PMC article.
-
Quantitative Proteomics Reveals Manganese Alleviates Heat Stress of Broiler Myocardial Cells via Regulating Nucleic Acid Metabolism.Biol Trace Elem Res. 2024 Mar;202(3):1187-1202. doi: 10.1007/s12011-023-03731-y. Epub 2023 Jun 27. Biol Trace Elem Res. 2024. PMID: 37369963
-
Pharmacoinformatic and molecular docking studies reveal potential novel antidepressants against neurodegenerative disorders by targeting HSPB8.Drug Des Devel Ther. 2016 May 6;10:1605-18. doi: 10.2147/DDDT.S101929. eCollection 2016. Drug Des Devel Ther. 2016. PMID: 27226709 Free PMC article.
Publication types
MeSH terms
Substances
Grants and funding
LinkOut - more resources
Full Text Sources
Other Literature Sources
Molecular Biology Databases
Miscellaneous