p38 Mitogen-Activated Protein Kinase Mediates Hyperosmolarity-Induced Vasoconstriction through Myosin Light Chain Phosphorylation and Actin Polymerization in Rat Aorta
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- Sasahara Tomoya
- Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin University
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- Yayama Katsutoshi
- Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin University
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- Okamoto Hiroshi
- Laboratory of Cardiovascular Pharmacology, Department of Biopharmaceutical Sciences, Kobe Gakuin University
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Hyperosmotic stress induces the contractile response of vascular smooth muscle cells (VSMCs). Previous studies have demonstrated that cytoskeleton reorganization and Rho/Rho-kinase-mediated inactivation of myosin light chain phosphatase (MLCP) play an important role in hyperosmotic vasoconstriction, but the precise mechanism is unknown. This study aimed to investigate the contractile response of endothelium-denuded rings of rat aortas to hyperosmolar sucrose (160 mM) in the presence or absence of inhibitors for various protein kinases. We found that the hyperosmotic constriction of aortic rings was attenuated not only by ML-7 or hydroxyfasudil, specific inhibitor for myosin light chain kinase (MLCK) or Rho-kinase, respectively, but also by SB203580, a specific inhibitor for p38 mitogen-activated kinase (p38 MAPK). Hyperosmolar sucrose evoked a transient increase in cytosolic free Ca2+ in rat VSMCs, and this response was not affected by SB203580. Western blot analysis of proteins extracted from rings showed that the hyperosmolar sucrose stimulated phosphorylation of the Rho-kinase-mediated myosin phosphatase target subunit 1, myosin light chain (MLC), and p38 MAPK. The experiments performed using a combination of the kinase inhibitors showed that hyperosmolarity-induced MLC phosphorylation is partially mediated via the SB203580-sensitive pathway and is independent of both MLCK and Rho-kinase-mediated inactivation of MLCP. Furthermore, the hyperosmolarity-induced increase in the F-actin/G-actin ratio in rings was attenuated not only by hydroxyfasudil but also by SB203580. These results suggest that p38 MAPK is involved in hyperosmotic vasoconstriction via stimulation of MLC phosphorylation and cytoskeleton reorganization through pathways independent of activation of MLCK and/or Rho-kinase-mediated mechanisms.
収録刊行物
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- Biological & Pharmaceutical Bulletin
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Biological & Pharmaceutical Bulletin 36 (11), 1849-1856, 2013
公益社団法人 日本薬学会
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詳細情報 詳細情報について
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- CRID
- 1390001204633006080
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- NII論文ID
- 130003361550
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- NII書誌ID
- AA10885497
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- COI
- 1:STN:280:DC%2BC3sbisF2jtA%3D%3D
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- ISSN
- 13475215
- 09186158
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- NDL書誌ID
- 024957898
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- PubMed
- 23979516
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- 本文言語コード
- en
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- データソース種別
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- JaLC
- NDL
- Crossref
- PubMed
- CiNii Articles
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- 抄録ライセンスフラグ
- 使用不可