| Project/Area Number |
10670695
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Circulatory organs internal medicine
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| Research Institution | National Cardiovascular Center Research Institute |
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Principal Investigator |
SASAGURI Toshiyuki National Cardiovascular Center Research Institute, Department of Bioscience, Head, バイオサイエンス部, 室長 (30261209)
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| Project Period (FY) |
1998 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 1999: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | Vascular smooth muscle / αィイD21ィエD2 adrenergic receptor / Jak / STAT / Tyrosine phosphorylation / Cellular hypertrophy / 交感神経 / アドレナリン / α受容体 |
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| Research Abstract |
The Janus-activated kinase/signal transducers and activators of transcription pathway (Jak/STAT pathway) is an established signal transduction system for cytokines. This pathway is activated following stimulation of the type I angiotensin II (ATィイD21ィエD2) receptor in vascular smooth muscle cells. To examine whether this pathway is shared among other G-protein-coupled receptors, we studied the linkage between the αィイD21ィエD2 adrenergic receptor and this pathway. The αィイD21ィエD2 agonist phenylephrine (100nM) induced tyrosine phosphorylation of Jak2, Tyk2, and STAT1 in human umbilical artery smooth muscle cells. The phosphorylation of Jak2 was prevented by the αィイD21ィエD2 receptor antagonists prazosin and αィイD21BィエD2-specific chloroethylcolonidine, but not by αィイD21AィエD2-specific WB4101, and the phosphorylation of STAT1 was inhibited by prazosin and Jak2-specific tyrosine kinase inhibitor AG490. After stimulation with phenylephrine, Jak2 and STAT1 were found to associate with αィイD21BィエD2 receptor. Phenylephrine stimulated the DNA binding activity of STAT1. However, phenylephrine did not promote that of STAT3. Recently the Jak/STAT pathway has been suggested to play a key role in the development of cardiac myocyte hypertrophy induced by interleukin 6-related cytokines. Therefore we were interested in whether this pathway mediates vascular smooth muscle hypertrophy induced by αィイD21ィエD2 agonists. Protein synthesis promoted by phenylephrine was inhibited by prazosin, AG490, and the introduction of a decoy oligonucleotide for STAT1. However a decoy for STAT3 was ineffective. These results suggested that αィイD21ィエD2 agonist stimulates STAT1 through activation of Jak2 and Tyk2 and that this pathway mediates αィイD21ィエD2 agonist-induced smooth muscle hypertrophy.
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