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dc.contributor.authorDuckles, H.*
dc.contributor.authorBoycott, H.E.*
dc.contributor.authorAl-Owais, M.M.*
dc.contributor.authorElies, Jacobo*
dc.contributor.authorJohnson, E.*
dc.contributor.authorDallas, M.L.*
dc.contributor.authorPorter, K.E.*
dc.contributor.authorGiuntini, F.*
dc.contributor.authorBoyle, J.P.*
dc.contributor.authorScragg, J.L.*
dc.contributor.authorPeers, C.*
dc.date.accessioned2017-06-14T14:03:58Z
dc.date.available2017-06-14T14:03:58Z
dc.date.issued2015-02
dc.identifier.citationDuckles H, Boycott HE, Al-Owais MM et al (2015) Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels. Pflügers Archiv – European Journal of Physiology. 467(2): 415-427.en_US
dc.identifier.urihttp://hdl.handle.net/10454/12206
dc.descriptionYesen_US
dc.description.abstractInduction of the antioxidant enzyme heme oxygenase-1 (HO-1) affords cellular protection and suppresses proliferation of vascular smooth muscle cells (VSMCs) associated with a variety of pathological cardiovascular conditions including myocardial infarction and vascular injury. However, the underlying mechanisms are not fully understood. Over-expression of Cav3.2 T-type Ca2+ channels in HEK293 cells raised basal [Ca2+]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca2+]i levels were reduced to levels seen in non-transfected cells either by induction of HO-1 or exposure of cells to the HO-1 product, carbon monoxide (CO) (applied as the CO releasing molecule, CORM-3). In the aortic VSMC line A7r5, proliferation was also inhibited by induction of HO-1 or by exposure of cells to CO, and patch-clamp recordings indicated that CO inhibited T-type (as well as L-type) Ca2+ currents in these cells. Finally, in human saphenous vein smooth muscle cells, proliferation was reduced by T-type channel inhibition or by HO-1 induction or CO exposure. The effects of T-type channel blockade and HO-1 induction were non-additive. Collectively, these data indicate that HO-1 regulates proliferation via CO-mediated inhibition of T-type Ca2+ channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically.en_US
dc.description.sponsorshipThis work was supported by the British Heart Foundation.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttp://dx.doi.org/10.1007/s00424-014-1503-5en_US
dc.rights© The Author(s) 2014. This article is published with open access at Springerlink.com This article is distributed under the terms of the Creative Commons Attribution License which permits any use, distribution, and reproduction in any medium, provided the original author(s) and the source are credited.en_US
dc.subjectHeme oxygenase; Carbon monoxide; Calcium channel; Proliferation; Vascular smooth muscleen_US
dc.titleHeme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channelsen_US
dc.status.refereedYesen_US
dc.date.Accepted2014-03-14
dc.date.application2014-04-18
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2018-07-25T13:40:25Z


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