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https://hdl.handle.net/2440/23882
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dc.contributor.author | Keller, M. | - |
dc.contributor.author | Lidington, D. | - |
dc.contributor.author | Vogel, L. | - |
dc.contributor.author | Peter, B. | - |
dc.contributor.author | Sohn, H. | - |
dc.contributor.author | Pagano, P. | - |
dc.contributor.author | Pitson, S. | - |
dc.contributor.author | Spiegel, S. | - |
dc.contributor.author | Pohl, U. | - |
dc.contributor.author | Bolz, S. | - |
dc.date.issued | 2006 | - |
dc.identifier.citation | The FASEB Journal, 2006; 20(6):1-20 | - |
dc.identifier.issn | 0892-6638 | - |
dc.identifier.issn | 1530-6860 | - |
dc.identifier.uri | http://hdl.handle.net/2440/23882 | - |
dc.description | Published online February 13, 2006 | - |
dc.description.abstract | Myogenic vasoconstriction, an intrinsic response to elevated transmural pressure (TMP), requires the activation of sphingosine kinase (Sk1) and the generation of reactive oxygen species (ROS). We hypothesized that pressure-induced Sk1 signaling and ROS generation are functionally linked. Using a model of cannulated resistance arteries isolated from the hamster gracilis muscle, we monitored vessel diameter and smooth muscle cell (SMC) Ca²⁺ i (Fura-2) or ROS production (dichlorodihydrofluorescein). Elevation of TMP stimulated the translocation of a GFP-tagged Sk1 fusion protein from the cytosol to the plasma membrane, indicative of enzymatic activation. Concurrently, elevation of TMP initiated a rapid and transient production of ROS, which was enhanced by expression of wild-type Sk1 (hSkwt) and inhibited by its dominant-negative mutant (hSkG82D). Exogenous sphingosine-1-phosphate (S1P) also stimulated ROS generation is isolated vessels. Chemical (1μmol/L DPI), peptide (gp91ds-tat/gp91ds), and genetic (N17Rac) inhibition strategies indicated that NADPH oxidase was the source of the pressure-induced ROS. NADPH oxidase inhibition attenuated myogenic vasoconstriction and reduced the apparent Ca²⁺ sensitivity of the SMC contractile apparatus, without affecting Ca²⁺-independent, RhoAmediated vasoconstriction in response to exogenous S1P. Our results indicate a mandatory role for Sk1/S1P in mediating pressure-induced, NADPH oxidase-derived ROS formation. In turn, ROS generation appears to increase Ca²⁺ sensitivity, necessary for full myogenic vasoconstriction. | - |
dc.description.statementofresponsibility | Matthias Keller, Darcy Lidington, Lukas Vogel, Bernhard Friedrich Peter, Hae-Young Sohn, Patrick J. Pagano, Stuart Pitson, Sarah Spiegel, Ulrich Pohl, and Steffen-Sebastian Bolz | - |
dc.language.iso | en | - |
dc.publisher | Federation of American Societies for Experimental Biology | - |
dc.rights | ©2006 FASEB | - |
dc.source.uri | http://dx.doi.org/10.1096/fj.05-4075fje | - |
dc.subject | smooth muscle | - |
dc.subject | signal transduction | - |
dc.subject | transfection | - |
dc.subject | NADPH oxidase | - |
dc.subject | Ca²⁺ sensitization | - |
dc.title | Sphingosine kinase functionally links elevated transmural pressure and increased reactive oxygen species formation in resistance arteries | - |
dc.type | Journal article | - |
dc.identifier.doi | 10.1096/fj.05-4075fje | - |
pubs.publication-status | Published | - |
dc.identifier.orcid | Pitson, S. [0000-0002-9527-2740] | - |
Appears in Collections: | Agriculture, Food and Wine publications Aurora harvest 2 |
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