Linked Life Data

11595755

Source:http://linkedlifedata.com/resource/pubmed/id/11595755

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2001-10-11
pubmed:abstractText
Oxidative stress has been implicated in the pathogenesis of stroke, traumatic brain injuries, and neurodegenerative diseases affecting both neuronal and glial cells in the CNS. In this study we have demonstrated that reactive oxygen species (ROS) dramatically induce the expression of two neuropeptide genes, the opioid proenkephalin (pENK) and the opioid-related proorphanin FQ (pOFQ; also known as pronociceptin) in primary astrocytes. Hydrogen peroxide (H2O2) treatment dose-dependently increased pENK and pOFQ mRNA levels with a maximal effect ( approximately 15-fold increase) being detected at 50 microM concentration. Exposing the astrocyte cultures to hypoxia and subsequent re-oxygenation also led to a profound elevation of pOFQ and pENK mRNA levels. Western blot analysis and immunocytochemistry revealed that H2O2 treatment elicited the phosphorylation and nuclear translocation of ERK 1/2 and p38 MAP kinases. Blockade of the p38 or the ERK MAP kinase pathways (by SB202190 and PD98059, respectively) prevented the H2O2-induced increase in pENK and pOFQ mRNA levels indicating a central role for these cascades in the regulation of pOFQ and pENK genes in response to oxidative stress. Regulation of pOFQ and pENK gene expression by ERK and p38 activation may be mediated through the transcription factor cAMP-response element binding protein (CREB). We observed CREB phosphorylation in response to H2O2, which was also prevented by SB202190 and PD98059. The nuclear factor-kappaB (NF-kappaB) pathway appears to be involved exclusively in the induction of pOFQ transcription by H2O2, as NF-kappaB inhibitors antagonized the effect of oxidative stress on pOFQ, but not on pENK expression. The profound induction of these genes by oxidative stress and these other factors may suggest a role for orphanin FQ and enkephalin in injury and stress responses of the CNS and neuropathophysiological conditions involving reactive oxygen species.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
79
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
35-44
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:11595755-Animals, pubmed-meshheading:11595755-Astrocytes, pubmed-meshheading:11595755-Biological Transport, pubmed-meshheading:11595755-Blotting, Western, pubmed-meshheading:11595755-Cell Nucleus, pubmed-meshheading:11595755-Cyclic AMP Response Element-Binding Protein, pubmed-meshheading:11595755-Enkephalins, pubmed-meshheading:11595755-Enzyme Activation, pubmed-meshheading:11595755-Gene Expression, pubmed-meshheading:11595755-Hydrogen Peroxide, pubmed-meshheading:11595755-Immunohistochemistry, pubmed-meshheading:11595755-Mitogen-Activated Protein Kinases, pubmed-meshheading:11595755-NF-kappa B, pubmed-meshheading:11595755-Oxidative Stress, pubmed-meshheading:11595755-Phosphorylation, pubmed-meshheading:11595755-Protein Precursors, pubmed-meshheading:11595755-RNA, Messenger, pubmed-meshheading:11595755-Rats, pubmed-meshheading:11595755-Rats, Sprague-Dawley, pubmed-meshheading:11595755-Receptors, Opioid, pubmed-meshheading:11595755-p38 Mitogen-Activated Protein Kinases
pubmed:year
2001
pubmed:articleTitle
Oxidative stress induces proorphanin FQ and proenkephalin gene expression in astrocytes through p38- and ERK-MAP kinases and NF-kappaB.
pubmed:affiliation
Department of Pharmacology, Uniformed Services University, Bethesda, Maryland 20814, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.