Linked Life Data

19654002

Source:http://linkedlifedata.com/resource/pubmed/id/19654002

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2009-8-31
pubmed:abstractText
We previously reported that reactive oxygen species (ROS) generated during hypoxia decrease hERG current density and protein expression in HEK cells stably expressing hERG protein. In the present study, we investigated the molecular mechanisms involved in hypoxia-induced downregulation of hERG protein. Culturing cells at low temperatures and addition of chemical chaperones during hypoxia restored hERG expression and currents to normoxic levels while antiarrhythmic drugs, which selectively block hERG channels, had no effect on hERG protein levels. Pulse chase studies showed that hypoxia blocks maturation of the core glycosylated form in the endoplasmic reticulum (ER) to the fully glycosylated form on the cell surface. Co-immunoprecipitation experiments revealed that hypoxia inhibited interaction of hERG with Hsp90 chaperone required for maturation, which was restored in the presence of ROS scavengers. These results demonstrate that ROS generated during hypoxia prevents maturation of the hERG protein by inhibiting Hsp90 interaction resulting in decreased protein expression and currents.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1090-2104
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
388
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
212-6
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Hypoxia inhibits maturation and trafficking of hERG K(+) channel protein: Role of Hsp90 and ROS.
pubmed:affiliation
Center for Systems Biology, Department of Medicine, The University of Chicago, Chicago, IL 60637, USA. jnanduri@uchicago.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural