論文 - 詳細
| RRC ID | 2488 |
|---|---|
| 著者 | Seguchi O, Takashima S, Yamazaki S, Asakura M, Asano Y, Shintani Y, Wakeno M, Minamino T, Kondo H, Furukawa H, Nakamaru K, Naito A, Takahashi T, Ohtsuka T, Kawakami K, Isomura T, Kitamura S, Tomoike H, Mochizuki N, Kitakaze M. |
| タイトル | A cardiac myosin light chain kinase regulates sarcomere assembly in the vertebrate heart. |
| ジャーナル | J Clin Invest |
| Abstract |
Marked sarcomere disorganization is a well-documented characteristic of cardiomyocytes in the failing human myocardium. Myosin regulatory light chain 2, ventricular/cardiac muscle isoform (MLC2v), which is involved in the development of human cardiomyopathy, is an important structural protein that affects physiologic cardiac sarcomere formation and heart development. Integrated cDNA expression analysis of failing human myocardia uncovered a novel protein kinase, cardiac-specific myosin light chain kinase (cardiac-MLCK), which acts on MLC2v. Expression levels of cardiac-MLCK were well correlated with the pulmonary arterial pressure of patients with heart failure. In cultured cardiomyocytes, knockdown of cardiac-MLCK by specific siRNAs decreased MLC2v phosphorylation and impaired epinephrine-induced activation of sarcomere reassembly. To further clarify the physiologic roles of cardiac-MLCK in vivo, we cloned the zebrafish ortholog z-cardiac-MLCK. Knockdown of z-cardiac-MLCK expression using morpholino antisense oligonucleotides resulted in dilated cardiac ventricles and immature sarcomere structures. These results suggest a significant role for cardiac-MLCK in cardiogenesis. |
| 巻・号 | 117(10) |
| ページ | 2812-24 |
| 公開日 | 2007-10-1 |
| DOI | 10.1172/JCI30804 |
| PMID | 17885681 |
| PMC | PMC1978424 |
| MeSH | Adult Aged Amino Acid Sequence Animals Cardiac Myosins / metabolism Cardiac Output, Low / enzymology* Cardiac Output, Low / genetics Cardiac Output, Low / pathology Cells, Cultured Cloning, Molecular Embryo, Nonmammalian / metabolism Female Heart / embryology* Humans Male Middle Aged Molecular Sequence Data Myocardium / enzymology Myocardium / ultrastructure* Myocytes, Cardiac / metabolism Myocytes, Cardiac / ultrastructure Myosin Light Chains / metabolism Myosin-Light-Chain Kinase / antagonists & inhibitors Myosin-Light-Chain Kinase / genetics Myosin-Light-Chain Kinase / metabolism* Myosin-Light-Chain Kinase / physiology* Oligonucleotide Array Sequence Analysis Oligoribonucleotides, Antisense / pharmacology Organogenesis* / genetics Rats Sarcomeres / metabolism* Up-Regulation Zebrafish / embryology Zebrafish / genetics Zebrafish / metabolism Zebrafish Proteins / antagonists & inhibitors Zebrafish Proteins / genetics Zebrafish Proteins / physiology* |
| IF | 11.864 |
| 引用数 | 99 |
| WOS 分野 | MEDICINE, RESEARCH & EXPERIMENTAL |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 最多言及媒体 | Wikipedia |
| 各媒体での言及数の合計 | 11 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ゼブラフィッシュ | SAG4A |