American journal of physiology. Regulatory, integrative and comparative physiology, 2009-02, Vol.296 (2), p.R201-R207
2009
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- Autor(en) / Beteiligte
- Titel
- Bradykinin regulates calpain and proinflammatory signaling through TRPM7-sensitive pathways in vascular smooth muscle cells
- Ist Teil von
- American journal of physiology. Regulatory, integrative and comparative physiology, 2009-02, Vol.296 (2), p.R201-R207
- Ort / Verlag
- United States: American Physiological Society
- Erscheinungsjahr
- 2009
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 1 Kidney Research Centre, Ottawa Health Research Institute, University of Ottawa, Ontario, Canada, 2 Insitute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil Submitted 15 July 2008 ; accepted in final form 10 September 2008 Transient receptor potential melastatin-7 (TRPM7) channels have recently been identified to be regulated by vasoactive agents acting through G protein-coupled receptors in vascular smooth muscle cells (VSMC). However, downstream targets and functional responses remain unclear. We investigated the subcellular localization of TRPM7 in VSMCs and questioned the role of TRPM7 in proinflammatory signaling by bradykinin. VSMCs from Wistar-Kyoto rats were studied. Cell fractionation by sucrose gradient and differential centrifugation demonstrated that in bradykinin-stimulated cells, TRPM7 localized in fractions corresponding to caveolae. Immunofluorescence confocal microscopy revealed that TRPM7 distributes along the cell membrane, that it has a reticular-type intracellular distribution, and that it colocalizes with flotillin-2, a marker of lipid rafts. Bradykinin increased expression of calpain, a TRPM7 target, and stimulated its cytosol/membrane translocation, an effect blocked by 2-APB (TRPM7 inhibitor) and U-73122 (phospholipase C inhibitor), but not by chelerythrine (PKC inhibitor). Expression of proinflammatory mediators VCAM-1 and cyclooxygenase-2 (COX-2) was time-dependently increased by bradykinin. This effect was blocked by Hoe-140 (B 2 receptor blocker) and 2-APB. Our data demonstrate that in bradykinin-stimulated VSMCs: 1 ) TRPM7 is upregulated, 2 ) TRPM7 associates with cholesterol-rich microdomains, and 3 ) calpain and proinflammatory mediators VCAM-1 and COX2 are regulated, in part, via TRPM7- and phospholipase C-dependent pathways through B 2 receptors. These findings identify a novel signaling pathway for bradykinin, which involves TRPM7. Such phenomena may play a role in bradykinin/B 2 receptor-mediated inflammatory responses in vascular cells. TRP channels; inflammation; signal transduction; bradykinin receptors; vascular cells Address for reprint requests and other correspondence: R. M. Touyz, Kidney Research Centre, Univ. of Ottawa/Ottawa Health Research Institute, 451 Smyth Rd. Ottawa, ON, Canada KIH 8M5 (e-mail: rtouyz{at}uottawa.ca )
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0363-6119eISSN: 1522-1490DOI: 10.1152/ajpregu.90602.2008Titel-ID: cdi_proquest_journals_229732273
- Format
- –
- Schlagworte
- Animals, Benzophenanthridines - pharmacology, Boron Compounds - pharmacology, Bradykinin - analogs & derivatives, Bradykinin - metabolism, Bradykinin - pharmacology, Bradykinin B2 Receptor Antagonists, Calpain - metabolism, Caveolae - metabolism, Cells, Cells, Cultured, Cyclooxygenase 2 - metabolism, Enzyme Inhibitors - pharmacology, Estrenes - pharmacology, Inflammation Mediators - metabolism, Magnesium - metabolism, Mesenteric Arteries - immunology, Mesenteric Arteries - metabolism, Muscle, Smooth, Vascular - drug effects, Muscle, Smooth, Vascular - enzymology, Muscle, Smooth, Vascular - immunology, Muscle, Smooth, Vascular - metabolism, Myocytes, Smooth Muscle - drug effects, Myocytes, Smooth Muscle - enzymology, Myocytes, Smooth Muscle - immunology, Myocytes, Smooth Muscle - metabolism, Peptides, Physiology, Proteases, Protein Kinase C - antagonists & inhibitors, Protein Kinase C - metabolism, Protein Transport, Proteins, Pyrrolidinones - pharmacology, Rats, Rats, Inbred WKY, Receptor, Bradykinin B2 - metabolism, Rodents, Signal transduction, Signal Transduction - drug effects, TRPM Cation Channels - antagonists & inhibitors, TRPM Cation Channels - metabolism, Type C Phospholipases - antagonists & inhibitors, Type C Phospholipases - metabolism, Up-Regulation, Vascular Cell Adhesion Molecule-1 - metabolism