TNNI3K, a Cardiac-Specific Kinase, Promotes Physiological Cardiac Hypertrophy in Transgenic Mice

Wang, Xiaojian; Wang, Jizheng; Su, Ming; Wang, Changxin; Chen, Jingzhou; Wang, Hu; Song, Lei; Zou, Yubao; Zhang, Lianfeng; Zhang, Youyi; Hui, Rutai
March 2013
PLoS ONE;Mar2013, Vol. 8 Issue 3, p1
Academic Journal
Purpose: Protein kinase plays an essential role in controlling cardiac growth and hypertrophic remodeling. The cardiac troponin I-interacting kinase (TNNI3K), a novel cardiac specific kinase, is associated with cardiomyocyte hypertrophy. However, the precise function of TNNI3K in regulating cardiac remodeling has remained controversial. Methods and Results: In a rat model of cardiac hypertrophy generated by transverse aortic constriction, myocardial TNNI3K expression was significantly increased by 1.62 folds (P<0.05) after constriction for 15 days. To investigate the role of TNNI3K in cardiac hypertrophy, we generated transgenic mouse lines with overexpression of human TNNI3K specifically in the heart. At the age of 3 months, the high-copy-number TNNI3K transgenic mice demonstrated a phenotype of concentric hypertrophy with increased heart weight normalized to body weight (1.31 fold, P<0.01). Echocardiography and non-invasive hemodynamic assessments showed enhanced cardiac function. No necrosis or myocyte disarray was observed in the heart of TNNI3K transgenic mice. This concentric hypertrophy maintained up to 12 months of age without cardiac dysfunction. The phospho amino acid analysis revealed that TNNI3K is a protein-tyrosine kinase. The yeast two-hybrid screen and co-immunoprecipitation assay identified cTnI as a target for TNNI3K. Moreover, TNNI3K overexpression induced cTnI phosphorylation at Ser22/Ser23 in vivo and in vitro, suggesting that TNNI3K is a novel upstream regulator for cTnI phosphorylation. Conclusion: TNNI3K promotes a concentric hypertrophy with enhancement of cardiac function via regulating the phosphorylation of cTnI. TNNI3K could be a potential therapeutic target for preventing from heart failure.


Related Articles

  • Targeted Sprouty1 overexpression in cardiac myocytes does not alter myocardial remodeling or function. Charles, Nathan; Huebert, Robert; Lee, Sangjin; Adhikari, Neeta; Polster, Sean; Rider, James; Braunlin, Elizabeth; Mariash, Ami; Robledo, Maggie; Schuweiler, David; Hall, Jennifer // Molecular & Cellular Biochemistry;Sep2010, Vol. 342 Issue 1/2, p57 

    The mitogen activated protein kinase (MAPK) signaling pathway regulates multiple events leading to heart failure including ventricular remodeling, contractility, hypertrophy, apoptosis, and fibrosis. The regulation of conserved intrinsic inhibitors of this pathway is poorly understood. We...

  • Role of Mitogen-Activated Protein Kinase Pathways in Multifactorial Adverse Cardiac Remodeling Associated with Metabolic Syndrome. Asrih, Mohamed; Mach, François; Nencioni, Alessio; Dallegri, Franco; Quercioli, Alessandra; Montecucco, Fabrizio // Mediators of Inflammation;2013, Vol. 2013, p1 

    Metabolic syndrome has been widely associated with an increased risk for acute cardiovascular events. Emerging evidence supports metabolic syndrome as a condition favoring an adverse cardiac remodeling, which might evolve towards heart dysfunction and failure. This pathological remodeling has...

  • Epigenetic control of signaling networks involved in interleukin-18-induced cardiac hypertrophy and its attenuation by pan-histone deacetylase inhibitors.  // BMC Bioinformatics;2010 Supplement 4, Vol. 11, p1 

    The article reports on a study that examines the epigenetic control of signaling networks in interleukin-18-induced cardiac hypertrophy and its attenuation by pan-histone deacetylase inhibitors (HDACIs) in mice. It highlights the accompaniment of preprogrammed cardiac hypertrophy-specific gene...

  • β-Adrenergic receptor stimulation causes cardiac hypertrophy via a Gβγ/Erk-dependent pathway. Vidal, Marie; Wieland, Thomas; Lohse, Martin J.; Lorenz, Kristina // Cardiovascular Research;Nov2012, Vol. 96 Issue 2, p255 

    Aims Activation of the β1-adrenergic receptor and its G protein, Gs, induces cardiac hypertrophy. However, activation of classic Gαs effectors, adenylyl cyclases (AC) and protein kinase A, is not sufficient for induction of hypertrophy, which suggests the involvement of additional...

  • Subcellular remodelling may induce cardiac dysfunction in congestive heart failure. Naranjan S. Dhalla; Harjot K. Saini-Chohan; Delfin Rodriguez-Leyva; Vijayan Elimban; Melissa R. Dent; Paramjit S. Tappia // Cardiovascular Research;Feb2009, Vol. 81 Issue 3, p429 

    It is commonly held that cardiac remodelling, represented by changes in muscle mass, size, and shape of the heart, explains the progression of congestive heart failure (CHF). However, this concept does not provide any clear information regarding the development of cardiac dysfunction in CHF....

  • TRPC6 fulfills a calcineurin signaling circuit during pathologic cardiac remodeling. Kuwahara, Koichiro; Yanggan Wang; McAnally, John; Richardson, James A.; Bassel-Duby, Rhonda; Hill, Joseph A.; Olson, Eric N.; Wang, Yanggan // Journal of Clinical Investigation;Dec2006, Vol. 116 Issue 12, p3114 

    The heart responds to injury and chronic pressure overload by pathologic growth and remodeling, which frequently result in heart failure and sudden death. Calcium-dependent signaling pathways promote cardiac growth and associated changes in gene expression in response to stress. The...

  • Integrin-linked kinase: Not so 'pseudo' after all. Hannigan, G E; McDonald, P C; Walsh, M P; Dedhar, S // Oncogene;10/27/2011, Vol. 30 Issue 43, p4375 

    Integrin-linked kinase (ILK) is a highly evolutionarily conserved intracellular protein that was originally identified as an integrin-interacting protein, and extensive genetic and biochemical studies have shown that ILK expression is vital during both embryonic development and tissue...

  • Pak6 protein kinase is a novel effector of an atypical Rho family GTPase Chp/RhoV. Shepelev, M.; Korobko, I. // Biochemistry (00062979);Jan2012, Vol. 77 Issue 1, p26 

    Chp/RhoV is an atypical Rho GTPase whose functions are far from being fully understood. To date several effector proteins of Chp have been identified, including p21-activated kinases Pak1, Pak2, and Pak4. Using a yeast two-hybrid system and co-immunoprecipitation, here we show that another...

  • The CBL-interacting protein kinase CIPK26 is a novel interactor of Arabidopsis NADPH oxidase AtRbohF that negatively modulates its ROS-producing activity in a heterologous expression system. Kimura, Sachie; Kawarazaki, Tomoko; Nibori, Hitomi; Michikawa, Masataka; Imai, Aya; Kaya, Hidetaka; Kuchitsu, Kazuyuki // Journal of Biochemistry;Feb2013, Vol. 153 Issue 2, p191 

    The plant NADPH oxidases, known as respiratory burst oxidase homologues (Rbohs), play an indispensable role in a wide array of cellular and developmental processes. Arabidopsis thaliana RbohF (AtRbohF)-mediated production of reactive oxygen species (ROS) is involved in biotic and abiotic stress...


Read the Article


Sorry, but this item is not currently available from your library.

Try another library?
Sign out of this library

Other Topics