Linked Life Data

8914025

Source:http://linkedlifedata.com/resource/pubmed/id/8914025

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1997-3-4
pubmed:abstractText
Oxidized low-density lipoprotein (Ox-LDL) is present in the lesions of focal segmental glomerulosclerosis (FSGS), but the role of Ox-LDL in the disease process is not clear. Recent studies have shown that LDL stimulates the type IV collagen mRNA expression in cultured mesangial cells. Thus, we examined whether oxidative stress is responsible for the stimulation of LDL-induced collagen gene expression in cultured human mesangial cells (HMCs). When quiescent HMCs were exposed to serum-free media containing LDL for 48 hours, peroxidation of LDL was induced as shown by the increased production of thiobarbituric acid-reactive substances (TBARS). LDL stimulated the alpha 1 (I), alpha 1 (III), and alpha 1 (IV) mRNA expression in a dose-dependent manner. At a concentration of 200 micrograms/ml, LDL enhanced the levels of alpha 1 (I), alpha 1 (III), and alpha 1 (IV) mRNA by 3.7-, 3.8- and 3.2-fold, respectively, over the levels in the control cells. These transcripts were further increased 5.4-, 6.7-, and 5.9-fold, respectively, by the addition of 500 micrograms/ml of LDL. Cu(2+)-catalyzed Ox-LDL at a concentration of 200 micrograms/ml also stimulated the alpha 1 (I), alpha 1 (III), and alpha 1 (IV) mRNA expression 4.4-, 5.9-, and 2.8-fold, respectively, compared with the control cells. The addition of monoclonal antibody (mAb) OL-10, which recognizes the malondialdehyde (MDA)-modified peptide epitope, or vitamin E (50 microM) to cultured HMC exposed to LDL markedly inhibited the stimulation of collagen gene expression. When HMCs were incubated with MDA (200 microM), alpha 1 (I), alpha 1 (III), and alpha 1 (IV) mRNA levels increased by two- to threefold compared to control cells. Immunohistochemical staining utilizing mAb OL-10 demonstrated the presence of MDA-modified proteins in the cytoplasm of HMC exposed to either LDL or MDA. These results suggest that peroxidative products of LDL stimulate collagen gene expression possibly via modification of proteins, which are responsible for the expression of collagen genes in cultured HMCs. Given that, lipid peroxidation of LDL may be implicated in the development of glomerulosclerosis by facilitating excessive mesangial matrix generation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0085-2538
pubmed:author
pubmed:issnType
Print
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1582-90
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:8914025-Antibodies, Monoclonal, pubmed-meshheading:8914025-Antioxidants, pubmed-meshheading:8914025-Blotting, Western, pubmed-meshheading:8914025-Cells, Cultured, pubmed-meshheading:8914025-Collagen, pubmed-meshheading:8914025-Copper, pubmed-meshheading:8914025-DNA, pubmed-meshheading:8914025-DNA Probes, pubmed-meshheading:8914025-Gene Expression Regulation, pubmed-meshheading:8914025-Glomerular Mesangium, pubmed-meshheading:8914025-Humans, pubmed-meshheading:8914025-Immunohistochemistry, pubmed-meshheading:8914025-Lipid Peroxidation, pubmed-meshheading:8914025-Lipoproteins, LDL, pubmed-meshheading:8914025-Oxidation-Reduction, pubmed-meshheading:8914025-Oxidative Stress, pubmed-meshheading:8914025-Polymerase Chain Reaction, pubmed-meshheading:8914025-Stimulation, Chemical
pubmed:year
1996
pubmed:articleTitle
Involvement of oxidation in LDL-induced collagen gene regulation in mesangial cells.
pubmed:affiliation
Department of Pathology, Seoul National University College of Medicine, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't