Linked Life Data

15183012

Source:http://linkedlifedata.com/resource/pubmed/id/15183012

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-6-8
pubmed:abstractText
Previously, we demonstrated that the organochlorine pesticide dieldrin induces mitochondrial depolarization, caspase-3 activation and apoptosis in dopaminergic PC12 cells. We also demonstrated that protein kinase Cdelta (PKCdelta), a member of a novel PKC family of proteins, is proteolytically activated by caspase-3 to mediate apoptotic cell death processes. In the present study, we have further characterized the protective effect of the major mitochondrial anti-apoptotic protein Bcl-2 against dieldrin-induced apoptotic events in dopaminergic cells. Exposure to dieldrin (30-100 microM) produced significant cytotoxicity and caspase-3 activation within 3h in vector-transfected PC12 cells, whereas human Bcl-2-transfected PC12 cells were almost completely resistant to dieldrin-induced cytotoxicity and caspase-3 activation. Also, dieldrin (30-300 microM) treatment induced proteolytic cleavage of poly(ADP-ribose) polymerase (PARP), which was blocked by pretreatment with caspase-3 inhibitors Z-DEVD-FMK and Z-VAD-FMK. Additionally, dieldrin-induced chromatin condensation and DNA fragmentation were completely blocked in Bcl-2-overexpressed PC12 cells as compared to vector control cells. Together, these results clearly indicate that overexpression of mitochondrial anti-apoptotic protein protects against dieldrin-induced apoptotic cell death and further suggest that dieldrin primarily alters mitochondrial function to initiate apoptotic cell death in dopaminergic cells.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0161-813X
pubmed:author
pubmed:issnType
Print
pubmed:volume
25
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
589-98
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Dieldrin promotes proteolytic cleavage of poly(ADP-ribose) polymerase and apoptosis in dopaminergic cells: protective effect of mitochondrial anti-apoptotic protein Bcl-2.
pubmed:affiliation
Parkinson's Disorder Research Laboratory, Department of Biomedical Sciences, Iowa State University, 2062 Veterinary Medicine Building, Ames, IA 50011-1250 USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.