Linked Life Data

19715754

Source:http://linkedlifedata.com/resource/pubmed/id/19715754

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2009-10-26
pubmed:abstractText
Oxidative stress leads to the disruption of calcium homeostasis in brain neurons; however, the direct effects of oxidants on proteins that regulate intracellular calcium ([Ca(2+)](i)) are not known. The calmodulin (CaM)-stimulated plasma membrane Ca(2+)-ATPase (PMCA) plays a critical role in regulating [Ca(2+)](i). Our previous in vitro studies showed that PMCA present in brain synaptic membranes is readily inactivated by a variety of reactive oxygen species (ROS). The present studies were conducted to determine the vulnerability of PMCA to ROS generated in neurons as would probably occur in vivo. Primary cortical neurons were exposed to paraquat (PQ), a redox cycling agent that generates intracellular ROS. Low concentrations of PQ (5-10 microM) increased PMCA basal activity by two-fold but abolished its sensitivity to CaM. Higher concentrations (25-100 microM) inhibited both components of PMCA activity. Immunoblots showed the formation of high-molecular-weight PMCA aggregates. Additionally, PMCA showed evidence of proteolytic degradation. PMCA proteolysis was prevented by a calpain inhibitor, suggesting a role for calpain. Our findings suggest that PMCA is a sensitive target of oxidative stress in primary neurons. Inactivation of this Ca(2+) transporter under prolonged oxidative stress could alter neuronal Ca(2+) signaling.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1873-4596
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1507-14
pubmed:dateRevised
2010-12-3
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Effects of paraquat-induced oxidative stress on the neuronal plasma membrane Ca(2+)-ATPase.
pubmed:affiliation
Department of Pharmacology and Toxicology, University of Kansas, Lawrence, KS 66045, USA. Azaidi@kcumb.edu
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural