Linked Life Data

14603533

Source:http://linkedlifedata.com/resource/pubmed/id/14603533

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2003-11-6
pubmed:abstractText
Pyrrolidine dithiocarbamate (PDTC), a metal chelating compound, is known to induce cell death in vascular smooth muscle cells (VSMC). However, the molecular mechanism for PDTC-induced VSMC death is not well understood. Addition of PDTC reduced cell growth and DNA synthesis on VSMC in low density conditions. However, in serum depleted medium, PDTC did not affect the cell viability, suggesting that certain factors in serum may mediate the cytotoxic effect of PDTC. Several metal chelators prevented the cell death induced by PDTC. In a serum-deprived condition, addition of exogenous metals, copper, iron, and zinc, restored the cytotoxic effect of PDTC. These data indicate that metals such as copper, iron, and zinc in serum may mediate the cytotoxic effect of PDTC. At low VSMC density in 10% FBS, treatment of PDTC, which induced a cell-cycle block in G1-phase, induced down-regulation of cyclins and CDKs and up-regulation of the CDK inhibitor p21 expression, whereas up-regulation of p27 or p53 by PDTC was not observed. Finally, we determined PDTC-mediated signaling pathway involved in VSMC death. Among relevant pathways, PDTC induced marked activation of p38MAPK and JNK. Expression of dominant negative p38MAPK and SB203580, a p38MAPK specific inhibitor, blocked PDTC-dependent p38MAPK, growth inhibition, and p21 expression. These data demonstrate that the p38MAPK pathway participates in p21 induction, which consequently leads to decrease of cyclin D1/cdk4 and cyclin E/cdk2 complexes and PDTC-dependent VSMC growth inhibition. In conclusion, an understanding of the molecular mechanisms of PDTC in VSMC provides a theoretical basis for clinical approaches using antioxidant therapies in atherosclerosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0021-9541
pubmed:author
pubmed:copyrightInfo
Copyright 2003 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
198
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
310-23
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:14603533-Animals, pubmed-meshheading:14603533-Apoptosis, pubmed-meshheading:14603533-Blotting, Western, pubmed-meshheading:14603533-Chelating Agents, pubmed-meshheading:14603533-Cyclin D1, pubmed-meshheading:14603533-Cyclin E, pubmed-meshheading:14603533-Cyclin-Dependent Kinase Inhibitor p21, pubmed-meshheading:14603533-Cyclins, pubmed-meshheading:14603533-G1 Phase, pubmed-meshheading:14603533-Male, pubmed-meshheading:14603533-Mitogen-Activated Protein Kinases, pubmed-meshheading:14603533-Muscle, Smooth, Vascular, pubmed-meshheading:14603533-Myocytes, Smooth Muscle, pubmed-meshheading:14603533-Precipitin Tests, pubmed-meshheading:14603533-Proline, pubmed-meshheading:14603533-Rats, pubmed-meshheading:14603533-Rats, Sprague-Dawley, pubmed-meshheading:14603533-Thiocarbamates, pubmed-meshheading:14603533-p38 Mitogen-Activated Protein Kinases
pubmed:year
2004
pubmed:articleTitle
PDTC, metal chelating compound, induces G1 phase cell cycle arrest in vascular smooth muscle cells through inducing p21Cip1 expression: involvement of p38 mitogen activated protein kinase.
pubmed:affiliation
National Research Laboratory for Glycobiology, Korean Ministry of Science and Technology, Kyungju, Kyungbuk, Korea.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't