Linked Life Data

19191707

Source:http://linkedlifedata.com/resource/pubmed/id/19191707

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2010-6-3
pubmed:abstractText
Plasmodium protozoa, the source of malarial infections, catabolize large quantities of hemoglobin during an intraerythrocytic phase. During this process, free heme is detoxified through biomineralization into an insoluble heme aggregate, hemozoin (Hz). In its native state, Hz is associated with a variety of lipid peroxidation products including 4-hydroxy-2-nonenal (HNE). In the present study, gene expression profiles were used to compare responses to two of the individual components of Hz in a model macrophage cell line. LPS-stimulated RAW 264.7 cells were exposed to HNE and the synthetic form of Hz, beta-hematin (BH), for 6 or 24 h. Microarray analysis identified alterations in gene expression induced by exposure to HNE and opsonized BH (fold change, > or = 1.8; p value, < or = 0.01). Patterns of gene expression were compared to changes induced by an opsonized control latex bead challenge in LPS-stimulated cells and revealed that the BH response was predominantly phagocytic. Ingenuity Pathway Analysis demonstrated that HNE mediated a short-term oxidative stress response and had a prolonged effect on the expression of genes associated with categories of "Cell Cycle", "Cellular Assembly and Organization", "DNA Replication, Recombination, and Repair", and "Cellular Development". Comparisons of expression changes caused by BH and HNE with those observed during malarial infection suggest that BH and HNE are involved in inflammatory response modulation, altered NF-kappaB signal transduction, extracellular matrix (ECM) degradation, and dyserythropoiesis. HNE exposure led to several significant steady-state expression changes including repressed chemokine (C-C motif) ligand 5 (Ccl5), indicative of dyserythropoiesis, and a severe matrix metalloproteinase 9 (Mmp9)/tissue inhibitor of metalloproteinase 1 (Timp1) imbalance in favor of ECM proteolysis.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-5010
pubmed:author
pubmed:issnType
Electronic
pubmed:day
16
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
433-45
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Comparative analysis of gene expression changes mediated by individual constituents of hemozoin.
pubmed:affiliation
Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, USA.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural