Linked Life Data

16488514

Source:http://linkedlifedata.com/resource/pubmed/id/16488514

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2006-5-15
pubmed:abstractText
Redox-active metals are of paramount importance for biological functions. Their impact and cellular activities participate in the physiological and pathophysiological processes of the central nervous system (CNS), including inflammatory responses. Manganese is an essential trace element and it is required for normal biological activities and ubiquitous enzymatic reactions. However, excessive chronic exposure to manganese results in neurobehavioral deficits. Recent evidence suggests that manganese neurotoxicity involves activation of microglia or astrocytes, representative CNS immune cells. In this study, we assessed the molecular basis of the effects of manganese on the modulation of pro-inflammatory cytokines and nitric oxide (NO) production in primary rat cortical glial cells. Cultured glial cells consisted of 85% of astrocytes and 15% of microglia. Within the assayed concentrations, manganese was unable to induce tumor necrosis factor alpha (TNF-alpha) and inducible nitric oxide synthase (iNOS) expression, whereas it potentiated iNOS and TNF-alpha gene expression by lipopolysaccharide/interferon-gamma-activated glial cells. The enhancement was accompanied by elevation of free manganese, generation of oxidative stress, activation of mitogen-activated protein kinases, and increased NF-kappaB and AP-1 binding activities. The potentiated degradation of inhibitory molecule IkappaB-alpha was one of underlying mechanisms for the increased activation of NF-kappaB by manganese. However, manganese decreased iNOS enzymatic activity possibly through the depletion of cofactor since exogenous tetrahydrobiopterin reversed manganese's action. These data indicate that manganese could modulate glial inflammation through variable strategies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0197-0186
pubmed:author
pubmed:issnType
Print
pubmed:volume
49
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
62-71
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:16488514-Animals, pubmed-meshheading:16488514-Astrocytes, pubmed-meshheading:16488514-Biopterin, pubmed-meshheading:16488514-Cells, Cultured, pubmed-meshheading:16488514-Cerebral Cortex, pubmed-meshheading:16488514-Cytokines, pubmed-meshheading:16488514-Encephalitis, pubmed-meshheading:16488514-Gene Expression Regulation, pubmed-meshheading:16488514-Gliosis, pubmed-meshheading:16488514-I-kappa B Proteins, pubmed-meshheading:16488514-Manganese, pubmed-meshheading:16488514-Manganese Poisoning, pubmed-meshheading:16488514-Microglia, pubmed-meshheading:16488514-NF-kappa B, pubmed-meshheading:16488514-Nitric Oxide, pubmed-meshheading:16488514-Nitric Oxide Synthase Type II, pubmed-meshheading:16488514-Oxidative Stress, pubmed-meshheading:16488514-RNA, Messenger, pubmed-meshheading:16488514-Rats, pubmed-meshheading:16488514-Rats, Sprague-Dawley, pubmed-meshheading:16488514-Up-Regulation
pubmed:year
2006
pubmed:articleTitle
Manganese modulates pro-inflammatory gene expression in activated glia.
pubmed:affiliation
Department of Education and Research, Taichung Veterans General Hospital, Taichung, Taiwan. cjchen@vghtc.gov.tw
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't