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rdf:type |
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lifeskim:mentions |
umls-concept:C0010453,
umls-concept:C0010749,
umls-concept:C0017641,
umls-concept:C0024432,
umls-concept:C0030685,
umls-concept:C0033268,
umls-concept:C0162638,
umls-concept:C0162772,
umls-concept:C0205263,
umls-concept:C0391871,
umls-concept:C0680255,
umls-concept:C1283071,
umls-concept:C1816452,
umls-concept:C1963578
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pubmed:issue |
1
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pubmed:dateCreated |
2001-11-7
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pubmed:abstractText |
The cytotoxicity and its underlying mechanisms induced by gliotoxin (GT), an immunosuppressive agent, in macrophages are poorly understood. We report here that GT induced a rapid apoptosis (DNA fragmentation and hypodiploid nuclei obtained within 4 hrs of treatment) in murine macrophages PU5-1.8 in a dose-dependent and cell cycle-independent manner. The GT-induced apoptosis was suppressed by z-Asp, z-VAD-fmk and antioxidants suggesting that production of reactive oxygen species (ROS) and activation of caspases were important in this process. Also, release of cytochrome c from mitochondria was found to be an early event (within 1 hr) after addition of GT (250 ng/ml) and its presence in the cytosol was sufficient to elicit apoptosis. Interestingly, the release of cytochrome c was not accompanied by a reduction in the mitochondrial membrane potential (psi m) as determined by several psi m-sensitive fluorescent indicators. Taken together, our results indicate that GT is a potent apoptotic agent in PU5-1.8 cells and the loss of psi m is not a universal early marker for apoptosis.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1071-5762
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
35
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1-10
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:11697112-Animals,
pubmed-meshheading:11697112-Antioxidants,
pubmed-meshheading:11697112-Apoptosis,
pubmed-meshheading:11697112-Blotting, Western,
pubmed-meshheading:11697112-Cell Cycle,
pubmed-meshheading:11697112-Cell Line,
pubmed-meshheading:11697112-Cytochrome c Group,
pubmed-meshheading:11697112-Ethidium,
pubmed-meshheading:11697112-Flow Cytometry,
pubmed-meshheading:11697112-Gliotoxin,
pubmed-meshheading:11697112-Hydrogen Peroxide,
pubmed-meshheading:11697112-Immunosuppressive Agents,
pubmed-meshheading:11697112-Macrophages,
pubmed-meshheading:11697112-Membrane Potentials,
pubmed-meshheading:11697112-Mice,
pubmed-meshheading:11697112-Mice, Inbred BALB C,
pubmed-meshheading:11697112-Mitochondria,
pubmed-meshheading:11697112-Reactive Oxygen Species,
pubmed-meshheading:11697112-Scopoletin
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pubmed:year |
2001
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pubmed:articleTitle |
Gliotoxin induces apoptosis in cultured macrophages via production of reactive oxygen species and cytochrome c release without mitochondrial depolarization.
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pubmed:affiliation |
Department of Biochemistry, Chinese University of Hong Kong, Shatin, Hong Kong, China.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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