Al-Owais, MM, Dallas, ML, Boyle, JP orcid.org/0000-0001-5786-6559 et al. (2 more authors) (2015) Heme Oxygenase-1 Influences Apoptosis via CO-mediated Inhibition of K+ Channels. In: Peers, C, Kumar, P, Wyatt, C, Gauda, E, Nurse, CA and Prabhakar, N, (eds.) Arterial Chemoreceptors in Physiology and Pathophysiology. Advances in Experimental Medicine and Biology, 860 . Springer International Publishing , Cham, Switzerland , pp. 343-351. ISBN 978-3-319-18439-5
Abstract
Hypoxic/ischemic episodes can trigger oxidative stress-mediated loss of central neurons via apoptosis, and low pO2 is also a feature of the tumor microenvironment, where cancer cells are particularly resistant to apoptosis. In the CNS, ischemic insult increases expression of the CO-generating enzyme heme oxygenase-1 (HO-1), which is commonly constitutively active in cancer cells. It has been proposed that apoptosis can be regulated by the trafficking and activity of K+ channels, particularly Kv2.1. We have explored the idea that HO-1 may influence apoptosis via regulation of Kv2.1. Overexpression of Kv2.1 in HEK293 cells increased their vulnerability to oxidant-induced apoptosis. CO (applied as the donor CORM-2) protected cells against apoptosis and inhibited Kv2.1 channels. Similarly in hippocampal neurones, CO selectively inhibited Kv2.1 and protected neurones against oxidant-induced apoptosis. In medulloblastoma sections we identified constitutive expression of HO-1 and Kv2.1, and in the medulloblastoma-derived cell line DAOY, hypoxic HO-1 induction or exposure to CO protected cells against apoptosis, and also selectively inhibited Kv2.1 channels expressed in these cells. These studies are consistent with a central role for Kv2.1 in apoptosis in both central neurones and cancer cells. They also suggest that HO-1 expression can strongly influence apoptosis via CO-mediated regulation of Kv2.1 activity.
Metadata
Item Type: | Book Section |
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Authors/Creators: |
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Editors: |
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Keywords: | Heme oxygenase; Carbon monoxide; Kv2.1 K+ channel; Neurone; Medulloblastoma; Apoptosis |
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: | 14 Oct 2016 08:40 |
Last Modified: | 14 Oct 2016 08:40 |
Published Version: | http://dx.doi.org/10.1007/978-3-319-18440-1_39 |
Status: | Published |
Publisher: | Springer International Publishing |
Series Name: | Advances in Experimental Medicine and Biology |
Identification Number: | 10.1007/978-3-319-18440-1_39 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:98722 |