Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels

Duckles, H., Boycott, H. E., Al-Owais, M. M., Elies, J., Johnson, E., Dallas, M. L. ORCID: https://orcid.org/0000-0002-5190-0522, Porter, K. E., Giuntini, F., Boyle, J. P., Scragg, J. L. and Peers, C. (2015) Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels. Pflugers Archive: European Journal of Physiology, 467 (2). pp. 415-427. ISSN 1432-2013 doi: 10.1007/s00424-014-1503-5

Abstract/Summary

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 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.

Item Type	Article
URI	https://reading-clone.eprints-hosting.org/id/eprint/36742
Identification Number/DOI	10.1007/s00424-014-1503-5
Refereed	Yes
Divisions	Interdisciplinary Research Centres (IDRCs) > Centre for Integrative Neuroscience and Neurodynamics (CINN) Life Sciences > School of Chemistry, Food and Pharmacy > School of Pharmacy > Division of Pharmacology
Uncontrolled Keywords	Heme oxygenase Carbon monoxide Calcium channel Proliferation Vascular smooth muscle
Publisher	Springer Berlin Heidelberg
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