Duckles, H, Boycott, HE, Al-Owais, MM et al. (8 more authors) (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). pp. 415-427. ISSN 0031-6768
Abstract
Induction 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 Ca(2+) channels in HEK293 cells raised basal [Ca(2+)]i and increased proliferation as compared with non-transfected cells. Proliferation and [Ca(2+)]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) Ca(2+) 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 Ca(2+) channels. This signalling pathway provides a novel means by which proliferation of VSMCs (and other cells) may be regulated therapeutically.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | (c) The Authors, 2014. Reproduced in accordance with the publisher's self-archiving policy. The final publication is available at Springer via http://dx.doi.org/10.1007/s00424-014-1503-5. |
Keywords: | Calcium Channel Blockers; Calcium Channels, T-Type; Carbon Monoxide; Cell Proliferation; HEK293 Cells; Heme Oxygenase-1; Myocytes, Smooth Muscle; Rats; Vascular smooth muscle |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Leeds Institute of Genetics, Health and Therapeutics (LIGHT) > Academic Unit of Cardiovascular Medicine (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 07 Jun 2016 15:51 |
Last Modified: | 16 Jan 2018 22:07 |
Published Version: | http://dx.doi.org/10.1007/s00424-014-1503-5 |
Status: | Published |
Publisher: | Springer Verlag |
Identification Number: | 10.1007/s00424-014-1503-5 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98707 |