Chapter title |
Heme Oxygenase-1 Influences Apoptosis via CO-mediated Inhibition of K(+) Channels.
|
---|---|
Chapter number | 39 |
Book title |
Arterial Chemoreceptors in Physiology and Pathophysiology
|
Published in |
Advances in experimental medicine and biology, January 2015
|
DOI | 10.1007/978-3-319-18440-1_39 |
Pubmed ID | |
Book ISBNs |
978-3-31-918439-5, 978-3-31-918440-1
|
Authors |
Al-Owais, Moza M, Dallas, Mark L, Boyle, John P, Scragg, Jason L, Peers, Chris, Moza M. Al-Owais, Mark L. Dallas, John P. Boyle, Jason L. Scragg, Chris Peers |
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. |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 11 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Postgraduate | 2 | 18% |
Other | 1 | 9% |
Lecturer | 1 | 9% |
Professor | 1 | 9% |
Student > Doctoral Student | 1 | 9% |
Other | 2 | 18% |
Unknown | 3 | 27% |
Readers by discipline | Count | As % |
---|---|---|
Medicine and Dentistry | 5 | 45% |
Environmental Science | 1 | 9% |
Neuroscience | 1 | 9% |
Pharmacology, Toxicology and Pharmaceutical Science | 1 | 9% |
Unknown | 3 | 27% |