Linked Life Data

10079214

Source:http://linkedlifedata.com/resource/pubmed/id/10079214

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-15
pubmed:abstractText
Lead (Pb) is a ubiquitous environmental contaminant that produces variety of effects on the central and peripheral nervous system, induces inflammatory response, and modulates immune functions. Though increase in lipid peroxidation and reactive oxygen intermediates (ROI) have been observed in Pb-induced toxicity, the molecular mechanism underlying these effects is largely unknown. Since nuclear factor kappa B (NF-kappaB) and activator protein (AP-1) are known to be activated by oxidative stress, we hypothesized that Pb-induced effects may be modulated via these transcription factors. The effects of Pb on NF-kappaB, AP-1, and related kinases were studied in pheochromocytoma cells (PC-12). Our results showed that treatment of murine PC-12 cells with Pb resulted in activation of NF-kappaB and degradation of IkappaBalpha (the inhibitory subunit of NF-kappaB). Pb-induced NF-kappaB dependent gene expression was also enhanced. The binding of Pb-induced NF-kappaB to DNA was blocked by antibodies for p65 and p50 but not by c-Rel or nonspecific antibodies such as cyclin D-1 and preimmune serum, suggesting that NF-kappaB consisted of p65 and p50 subunits. Similar to its effects on NF-kappaB, Pb also activated AP-1 in a time- and dose-dependent manner. Besides activating these transcription factors, Pb was also found to upregulate the related kinases such as mitogen activated protein kinase kinase (MEK) and c-Jun N-terminal kinase (JNK) (also known as stress-activated protein kinase) in a dose- and time-dependent manner. Thus, these results suggest that NF-kappaB, AP-1, MEK, and JNK may be important mediators of Pb-induced signaling in gene expression mediating inflammatory response and immunomodulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
155
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
280-6
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10079214-Animals, pubmed-meshheading:10079214-Blotting, Western, pubmed-meshheading:10079214-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10079214-Dose-Response Relationship, Drug, pubmed-meshheading:10079214-Electrophoresis, pubmed-meshheading:10079214-Gene Expression Regulation, Neoplastic, pubmed-meshheading:10079214-JNK Mitogen-Activated Protein Kinases, pubmed-meshheading:10079214-Lead, pubmed-meshheading:10079214-Mitogen-Activated Protein Kinase Kinases, pubmed-meshheading:10079214-Mitogen-Activated Protein Kinases, pubmed-meshheading:10079214-NF-kappa B, pubmed-meshheading:10079214-PC12 Cells, pubmed-meshheading:10079214-Protein Kinases, pubmed-meshheading:10079214-Rats, pubmed-meshheading:10079214-Time Factors, pubmed-meshheading:10079214-Transcription Factor AP-1, pubmed-meshheading:10079214-Transfection
pubmed:year
1999
pubmed:articleTitle
Lead activates nuclear transcription factor-kappaB, activator protein-1, and amino-terminal c-Jun kinase in pheochromocytoma cells.
pubmed:affiliation
College of Pharmacy and Health Sciences, Texas Southern University, Houston, Texas, 77004, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't