Overexpression of TNNI3K, a cardiac-specific MAP kinase, promotes P19CL6-derived cardiac myogenesis and prevents myocardial infarction-induced injury

Autor: Yu Zhen Chen, Nobuo Sakaguchi, Li Ping Feng, Xiao Shu Cheng, Jin Feng Ding, Ping Li, Lai Yuan Wang, Zhong-Fang Lai, Yasunori Kitamoto, Xian Min Meng, Issei Komuro, Jue Ye, Koshiro Monzen, Shokei Kim-Mitsuyama
Rok vydání: 2008
Předmět:
Male
Embryonal Carcinoma Stem Cells
Physiology
Myocardial Infarction
Action Potentials
Apoptosis
Muscle Development
p38 Mitogen-Activated Protein Kinases
Ventricular Function
Left
Mice
Actinin
Myocytes
Cardiac
Myocardial infarction
Annexin A5
Phosphorylation
Tyrosine
bcl-2-Associated X Protein
Ventricular Remodeling
Kinase
Myogenesis
Cell Differentiation
MAP Kinase Kinase Kinases
Cell biology
Mitogen-activated protein kinase
Circulatory system
cardiovascular system
Cardiology and Cardiovascular Medicine
Pluripotent Stem Cells
medicine.medical_specialty
Epinephrine
Molecular Sequence Data
Protein Serine-Threonine Kinases
Biology
Transfection
Cell Line
Tumor
Physiology (medical)
Internal medicine
medicine
Animals
Humans
Gene
Cell Proliferation
Troponin I
JNK Mitogen-Activated Protein Kinases
medicine.disease
Myocardial Contraction
Mice
Inbred C57BL
Disease Models
Animal
Endocrinology
biology.protein
Stem Cell Transplantation
Zdroj: American Journal of Physiology-Heart and Circulatory Physiology. 295:H708-H716
ISSN: 1522-1539
0363-6135
Popis: TNNI3K is a new cardiac-specific MAP kinase whose gene is localized to 1p31.1 and that belongs to a tyrosine kinase-like branch in the kinase tree of the human genome. In the present study we investigated the role of TNNI3K in the cardiac myogenesis process and in the repair of ischemic injury. Pluripotent P19CL6 cells with or without transfection by pcDNA6-TNNI3K plasmid were used to induce differentiation into beating cardiomyocytes. TNNI3K promoted the differentiation process, judging from the increasing beating mass and increased number of α-actinin-positive cells. TNNI3K improved cardiac function by enhancing beating frequency and increasing the contractile force and epinephrine response of spontaneous action potentials without an increase of the single-cell size. TNNI3K suppressed phosphorylation of cardiac troponin I, annexin-V+ cells, Bax protein, and p38/JNK-mediated apoptosis. Intramyocardial administration of TNNI3K-overexpressing P19CL6 cells in mice with myocardial infarction improved cardiac performance and attenuated ventricular remodeling compared with injection of wild-type P19CL6 cells. In conclusion, our study clearly indicates that TNNI3K promotes cardiomyogenesis, enhances cardiac performance, and protects the myocardium from ischemic injury by suppressing p38/JNK-mediated apoptosis. Therefore, modulation of TNNI3K activity would be a useful therapeutic approach for ischemic cardiac disease.
Databáze: OpenAIRE
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