Linked Life Data

21427056

Source:http://linkedlifedata.com/resource/pubmed/id/21427056

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-5-23
pubmed:abstractText
Aminochrome, the precursor of neuromelanin, has been proposed to be involved in the neurodegeneration neuromelanin-containing dopaminergic neurons in Parkinson's disease. We aimed to study the mechanism of aminochrome-dependent cell death in a cell line derived from rat substantia nigra. We found that aminochrome (50?M), in the presence of NAD(P)H-quinone oxidoreductase, EC 1.6.99.2 (DT)-diaphorase inhibitor dicoumarol (DIC) (100?M), induces significant cell death (62 ± 3%; p < 0.01), increase in caspase-3 activation (p < 0.001), release of cytochrome C, disruption of mitochondrial membrane potential (p < 0.01), damage of mitochondrial DNA, damage of mitochondria determined with transmission electron microscopy, a dramatic morphological change characterized as cell shrinkage, and significant increase in number of autophagic vacuoles. To determine the role of autophagy on aminochrome-induced cell death, we incubated the cells in the presence of vinblastine and rapamycin. Interestingly, 10?M vinblastine induces a 5.9-fold (p < 0.001) and twofold (p < 0.01) significant increase in cell death when the cells were incubated with 30?M aminochrome in the absence and presence of DIC, respectively, whereas 10?M rapamycin preincubated 24 h before addition of 50?M aminochrome in the absence and the presence of 100?M DIC induces a significant decrease (p < 0.001) in cell death. In conclusion, autophagy seems to be an important protective mechanism against two different aminochrome-induced cell deaths that initially showed apoptotic features. The cell death induced by aminochrome when DT-diaphorase is inhibited requires activation of mitochondrial pathway, whereas the cell death induced by aminochrome alone requires inhibition of autophagy-dependent degrading of damaged organelles and recycling through lysosomes.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1096-0929
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
376-88
pubmed:meshHeading
pubmed-meshheading:21427056-Animals, pubmed-meshheading:21427056-Autophagy, pubmed-meshheading:21427056-Caspase 3, pubmed-meshheading:21427056-Cell Death, pubmed-meshheading:21427056-Cell Line, pubmed-meshheading:21427056-Cytochromes c, pubmed-meshheading:21427056-DNA, Mitochondrial, pubmed-meshheading:21427056-Indolequinones, pubmed-meshheading:21427056-Melanins, pubmed-meshheading:21427056-Membrane Potential, Mitochondrial, pubmed-meshheading:21427056-Microscopy, Electron, Transmission, pubmed-meshheading:21427056-Mitochondria, pubmed-meshheading:21427056-NAD(P)H Dehydrogenase (Quinone), pubmed-meshheading:21427056-Nerve Degeneration, pubmed-meshheading:21427056-Rats, pubmed-meshheading:21427056-Sirolimus, pubmed-meshheading:21427056-Substantia Nigra, pubmed-meshheading:21427056-Vinblastine
pubmed:year
2011
pubmed:articleTitle
Autophagy protects against aminochrome-induced cell death in substantia nigra-derived cell line.
pubmed:affiliation
Program of Molecular and Clinical Pharmacology, Biomedical Science Institute, Faculty of Medicine, University of Chile, Santiago 8380453, Chile.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural