Linked Life Data

19657056

Source:http://linkedlifedata.com/resource/pubmed/id/19657056

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-10-2
pubmed:abstractText
Hypoxic inhibition of K+ current is a critical O2-sensing mechanism. Previously, it was demonstrated that the cooperative action of TASK-1 and NADPH oxidase-4 (NOX4) mediated the O2-sensitive K+ current response. Here we addressed the O2-sensing mechanism of NOX4 in terms of TASK-1 regulation. In TASK-1 and NOX4-coexpressing human embryonic kidney 293 cells, hypoxia (5% O2) decreased the amplitude of TASK-1 current (hypoxia-DeltaI(TASK-1)). To examine whether reactive oxygen species (ROS) mediate the hypoxia-DeltaI(TASK-1), we treated the cells with carbon monoxide (CO) which is known to reduce ROS generation from the heme-containing NOX4. Unexpectedly, CO failed to mimic hypoxia in TASK-1 regulation, rather blocked the hypoxia-DeltaI(TASK-1). Moreover, the hypoxia-DeltaI(TASK-1) was neither recovered by H2O2 treatment nor prevented by antioxidant such as ascorbic acid. However, the hypoxia-DeltaI(TASK-1) was noticeably attenuated by succinyl acetone, a heme synthase inhibitor. To further evaluate the role of heme, we constructed and expressed various NOX4 mutants, such as HBD(-) lacking the heme binding domain, NBD(-) lacking the NADPH binding domain, FBD(-) lacking the FAD binding domain, and HFBD(-) lacking both heme and FAD domains. The hypoxia-DeltaI(TASK-1) was significantly reduced in HBD(-)-, FBD(-)-, or HFBD(-)-expressing cells, versus wild-type NOX4-expressing cells. However, NBD(-) did not affect the TASK-1 response to hypoxia. We also found that p22 is required for the NOX4-dependent TASK-1 regulation. These results suggest that O2 binding with NOX4 per se controls TASK-1 activity. In this process, the heme moiety and FBD seem to be responsible for the NOX4 regulation of TASK-1, and p22 might support the NOX4-TASK-1 interaction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1522-1563
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
297
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C855-64
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Identification of subdomains in NADPH oxidase-4 critical for the oxygen-dependent regulation of TASK-1 K+ channels.
pubmed:affiliation
Department of Physiology, Seoul National University College of Medicine, Seoul National University, Seoul, Republic of Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't