論文 - 詳細
| RRC ID | 2809 |
|---|---|
| 著者 | Satoh S, Tanaka H, Ueda Y, Oyama J, Sugano M, Sumimoto H, Mori Y, Makino N. |
| タイトル | Transient receptor potential (TRP) protein 7 acts as a G protein-activated Ca2+ channel mediating angiotensin II-induced myocardial apoptosis. |
| ジャーナル | Mol Cell Biochem |
| Abstract |
Transient receptor potential (TRP) proteins have been identified as cation channels that are activated by agonist-receptor coupling and mediate various cellular functions. TRPC7, a homologue of TRP channels, has been shown to act as a Ca2+ channel activated by G protein-coupled stimulation and to be abundantly expressed in the heart with an as-yet-unknown function. We studied the role of TRPC7 in G protein-activated signaling in HEK293 cells and cultured cardiomyocytes in vitro transfected with FLAG-tagged TRPC7 cDNA and in Dahl salt-sensitive rats with heart failure in vivo. TRPC7-transfected HEK293 cells showed an augmentation of carbachol-induced intracellular Ca2+ transient, which was attenuated under a Ca2+-free condition or in the presence of SK&F96365 (a Ca2+-permeable channel blocker). Upon stimulation with angiotensin II (Ang II), cultured neonatal rat cardiomyocytes transfected with TRPC7 exhibited a significant increase in apoptosis detected by TUNEL staining, accompanied with a decrease in the expression of atrial natriuretic factor and destruction of actin fibers, as compared with non-transfected cardiomyocytes. Ang II-induced apoptosis was inhibited by CV-11974 (Candesartan; Ang II type 1 [AT1] receptor blocker), SK&F96365, and FK506 (calcineurin inhibitor). In Dahl salt-sensitive rats, apoptosis and TRPC7 expression were increased in the failing myocardium, and a long-term treatment with temocapril, an angiotensin-converting enzyme inhibitor, suppressed both. Our findings suggest that TRPC7 could act as a Ca2+ channel activated by AT1 receptors, leading to myocardial apoptosis possibly via a calcineurin-dependent pathway. TRPC7 might be a key initiator linking AT1-activation to myocardial apoptosis, and thereby contributing to the process of heart failure. |
| 巻・号 | 294(1-2) |
| ページ | 205-15 |
| 公開日 | 2007-1-1 |
| DOI | 10.1007/s11010-006-9261-0 |
| PMID | 16838106 |
| MeSH | Angiotensin II / pharmacology* Animals Animals, Newborn Apoptosis / drug effects* Calcium Channel Blockers / pharmacology Calcium Channels / genetics Calcium Channels / metabolism* Carbachol / pharmacology Cell Line Cells, Cultured Cholinergic Agonists / pharmacology GTP-Binding Proteins / metabolism* Heart Ventricles / cytology Humans Myocardium / cytology Myocytes, Cardiac / drug effects Rats Rats, Inbred Dahl Rats, Sprague-Dawley TRPC Cation Channels / genetics TRPC Cation Channels / metabolism* Transfection |
| IF | 2.795 |
| 引用数 | 63 |
| WOS 分野 | CELL BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
|
| 各媒体での言及数の合計 | 0 |
| リソース情報 | |
| ラット | SS/JrNgs(strainID=798) SR/JrNgs(strainID=799) |
| ヒト・動物細胞 | 293(RCB1637) |