Title |
Heme oxygenase-1 regulates cell proliferation via carbon monoxide-mediated inhibition of T-type Ca2+ channels
|
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Published in |
Pflügers Archiv - European Journal of Physiology, April 2014
|
DOI | 10.1007/s00424-014-1503-5 |
Pubmed ID | |
Authors |
Hayley Duckles, Hannah E. Boycott, Moza M. Al-Owais, Jacobo Elies, Emily Johnson, Mark L. Dallas, Karen E. Porter, Francesca Giuntini, John P. Boyle, Jason L. Scragg, Chris Peers |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
---|---|---|
Unknown | 34 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
---|---|---|
Student > Ph. D. Student | 5 | 15% |
Student > Master | 5 | 15% |
Student > Doctoral Student | 3 | 9% |
Student > Bachelor | 3 | 9% |
Researcher | 3 | 9% |
Other | 8 | 24% |
Unknown | 7 | 21% |
Readers by discipline | Count | As % |
---|---|---|
Agricultural and Biological Sciences | 8 | 24% |
Medicine and Dentistry | 6 | 18% |
Neuroscience | 3 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 2 | 6% |
Engineering | 2 | 6% |
Other | 5 | 15% |
Unknown | 8 | 24% |