Linked Life Data

15337317

Source:http://linkedlifedata.com/resource/pubmed/id/15337317

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-8-31
pubmed:abstractText
Oxidative stress has been implicated in neurotoxic damage associated with various metals, including methylmercury (MeHg). Although the mechanism(s) of MeHg-induced neurotoxicity remains unclear, evidence supports a mediatory role for astrocytes, a cell type that preferentially accumulates MeHg. Using scanning confocal microscopy (LSCM), the present study was undertaken to examine the role of astrocytes as the site of reactive oxygen species (ROS). Three redox-sensitive fluorescent probes were used for ROS analysis, (a) CM-H2DCFDA (chloromethyl derivative of dichlorodihydrofluorescein diacetate), a probe for intracellular hydrogen peroxide (H2O2); (b) hydroethidine (HETH), a probe for superoxide anion (*O2-), and (c) CM-H2XRos (chloromethyl derivative of dihydro X-rosamine), and a probe that is selective for mitochondrial reactive oxygen intermediates. Astrocytes were treated with 10 microM MeHg for 30 min, following which the various fluorescent probes were added; 20 min later LSCM images were collected. Astrocytes loaded with CM-H2DCFDA and HE demonstrated a significant MeHg-induced increase in fluorescence intensity indicative of increased intracellular H2O2 and *O2-, respectively. Similar results were obtained with the mitotracker dye, CM-H2XRos. Additionally, exposure of astrocytes for 24 h to 100 microM buthionine-L-sulfoxane (BSO), a glutathione (GSH) synthesis inhibitor, caused a significant increase in ROS formation. Furthermore, BSO pretreatment significantly enhanced the MeHg-induced formation of *O2-, indicating an important role for GSH in the maintenance of optimal cellular redox status. Time-course experiments performed in the simultaneous presence of CM-H2XRos and CM-H2DCFDA demonstrated that the MeHg-induced CM-H2XRos fluorescence changes preceded those of CM-H2DCFDA, suggesting that the mitochondria represent an early primary site for ROS formation. Taken together, these studies illustrate that MeHg induces the generation of astrocyte-derived ROS and support a role for astrocytic ROS in MeHg-associated neurotoxic damage.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
0169-328X
pubmed:author
pubmed:issnType
Print
pubmed:day
10
pubmed:volume
128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-57
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Free radical formation in cerebral cortical astrocytes in culture induced by methylmercury.
pubmed:affiliation
Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston-Salem, NC, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.