Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2009-4-13
pubmed:abstractText
Increasing evidence suggests that acetaminophen has unappreciated anti-oxidant and anti-inflammatory properties. Drugs that affect oxidant and inflammatory stress in the brain are of interest because both processes are thought to contribute to the pathogenesis of neurodegenerative disease. The objective of this study is to determine whether acetaminophen affects the response of brain endothelial cells to oxidative stress. Cultured brain endothelial cells are pre-treated with acetaminophen and then exposed to the superoxide-generating compound menadione (25 microM). Cell survival, inflammatory protein expression, and anti-oxidant enzyme activity are measured. Menadione causes a significant (p<0.001) increase in endothelial cell death as well as an increase in RNA and protein levels of tumor necrosis factor alpha, interleukin-1, macrophage inflammatory protein alpha, and RANTES. Menadione also evokes a significant (p<0.001) increase in the activity of the anti-oxidant enzyme superoxide dismutase (SOD). Pre-treatment of endothelial cell cultures with acetaminophen (25-100 microM) increases endothelial cell survival and inhibits menadione-induced expression of inflammatory proteins and SOD activity. In addition, we document, for the first time, that acetaminophen increases expression of the anti-apoptotic protein Bcl2. Suppressing Bcl2 with siRNA blocks the pro-survival effect of acetaminophen. These data show that acetaminophen has anti-oxidant and anti-inflammatory effects on the cerebrovasculature and suggest a heretofore unappreciated therapeutic potential for this drug in neurodegenerative diseases such as Alzheimer's disease that are characterized by oxidant and inflammatory stress.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-10422949, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-10818491, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-11562448, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-11605988, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-11770899, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-11918971, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-12011492, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-12153990, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-12605411, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-14557822, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-14625346, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-14643753, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-15151930, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-15618346, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-15705740, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16081117, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16638633, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16701773, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16831125, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16855872, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16859400, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-16863451, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-17305405, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-17439248, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-17606472, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-17638096, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-17724253, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-17921323, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-18054472, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-18514411, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-18700144, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-2499947, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-7503812, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-7528015, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-8140579, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-8825410, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-9299017, http://linkedlifedata.com/resource/pubmed/commentcorrection/19265712-9926361
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1095-9319
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
77
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
289-96
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed-meshheading:19265712-Acetaminophen, pubmed-meshheading:19265712-Animals, pubmed-meshheading:19265712-Anti-Inflammatory Agents, Non-Steroidal, pubmed-meshheading:19265712-Antioxidants, pubmed-meshheading:19265712-Apoptosis, pubmed-meshheading:19265712-Brain, pubmed-meshheading:19265712-Cell Survival, pubmed-meshheading:19265712-Cells, Cultured, pubmed-meshheading:19265712-Chemokines, pubmed-meshheading:19265712-Endothelium, Vascular, pubmed-meshheading:19265712-Gene Expression, pubmed-meshheading:19265712-Oxidative Stress, pubmed-meshheading:19265712-RNA, Messenger, pubmed-meshheading:19265712-RNA, Small Interfering, pubmed-meshheading:19265712-RNA Interference, pubmed-meshheading:19265712-Rats, pubmed-meshheading:19265712-Superoxide Dismutase, pubmed-meshheading:19265712-Vitamin K 3, pubmed-meshheading:19265712-bcl-Associated Death Protein
pubmed:year
2009
pubmed:articleTitle
Acetaminophen protects brain endothelial cells against oxidative stress.
pubmed:affiliation
Garrison Institute on Aging, Texas Tech University Health Sciences Center, 3601 4th Street Stop 9424, Lubbock, TX 79430, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural