Linked Life Data

21257924

Source:http://linkedlifedata.com/resource/pubmed/id/21257924

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2011-9-7
pubmed:abstractText
Asbestos is a naturally occurring fibrous silicate, whose inhalation is highly related to the risk of developing malignant mesothelioma (MM), and crocidolite is one of its most oncogenic types. The mechanism by which asbestos may cause MM is unclear. We have previously observed that crocidolite in human MM (HMM) cells induces NF-?B activation and stimulates the synthesis of nitric oxide by inhibiting the RhoA signaling pathway. In primary human mesothelial cells (HMCs) and HMM cells exposed to crocidolite asbestos, coincubated or not with antioxidants, we evaluated cytotoxicity and oxidative stress induction (lipid peroxidation) and the effect of asbestos on the RhoA signaling pathway (RhoA GTP binding, Rho kinase activity, RhoA prenylation, hydroxy-3-methylglutharyl-CoA reductase activity). In this paper we show that the reactive oxygen species generated by the incubation of crocidolite with primary HMCs and three HMM cell lines mediate the inhibition of 3-hydroxy-3-methylglutharyl-CoA reductase (HMGCR). The coincubation of HMCs and HMM cells with crocidolite together with antioxidants, such as Tempol, Mn-porphyrin, and the association of superoxide dismutase and catalase, prevented the cytotoxicity and lipoperoxidation caused by crocidolite alone as well as the decrease of HMGCR activity and restored the RhoA/RhoA-dependent kinase activity and the RhoA prenylation. The same effect was observed when the oxidizing agent menadione was administrated to the cells in place of crocidolite. Such a mechanism could at least partly explain the effects exerted by crocidolite fibers in mesothelial cells.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1535-4989
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
625-31
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Antioxidants prevent the RhoA inhibition evoked by crocidolite asbestos in human mesothelial and mesothelioma cells.
pubmed:affiliation
Department of Genetics, Biology and Biochemistry, University of Torino, Italy. elisabetta.aldieri@unito.it
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't