Source:http://linkedlifedata.com/resource/pubmed/id/20804509
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
12
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| pubmed:dateCreated |
2010-11-30
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| pubmed:abstractText |
1. Diallyl disulphide (DADS) has potential as a chemopreventive and therapeutic agent. Previous studies have reported that Ras-related C3 botulinum toxin substrate 2 (Rac2), a regulatory subunit of the NADPH oxidase complex, is upregulated in DADS-induced apoptosis in human leukaemia HL-60 cells. The aim of the present study was to investigate the role of Rac2, NADPH oxidase and reactive oxygen species (ROS) in DADS-induced apoptosis. 2. Expression of the Rac2 gene along with that of five other genes of NADPH oxidase subunits were in HL-60 cells measured by Sybergreen quantitative real-time polymerase chain reaction. RNA interference was used to test the effect of Rac2. Protein expression was evaluated using western blot analysis and ROS levels were measured by 2',7'-dichlorofluorescein diacetate (DCFH-DA) fluorescence. DNA fragmentation and flow cytometry analysis were used to detect apoptotic cells. 3. Levels of Rac2 gene and protein were significantly upregulated and NADPH oxidase was activated in DADS-induced apoptosis. Pretreatment of HL-60 cells with small interfering (si) RNAs to inhibit Rac2 blocked DADS-induced apoptosis. Diallyl disulphide-induced intracellular ROS production was increased in phorbol myristate acetate-stimulated cells, but decreased in Rac2 siRNA-treated cells. In Rac2 siRNA-treated cells, activator protein-1 and caspase 3 levels decreased, c-myc protein levels were increased and p38 protein levels were unchanged compared with Rac2-competent, DADS-treated cells. 4. These results demonstrate that NADPH oxidase is the main source of DADS-induced ROS. In addition, Rac2 selectively activates the c-Jun N-terminal kinase pathway, but not the p38 pathway, in DADS-induced apoptosis. So, Rac2, NADPH oxidase and ROS have a critical role in DADS-induced apoptosis in human leukaemia HL-60 cells.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Allyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Caspase 3,
http://linkedlifedata.com/resource/pubmed/chemical/Disulfides,
http://linkedlifedata.com/resource/pubmed/chemical/JNK Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/MYC protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/NADPH Oxidase,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-myc,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Reactive Oxygen Species,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factor AP-1,
http://linkedlifedata.com/resource/pubmed/chemical/diallyl disulfide,
http://linkedlifedata.com/resource/pubmed/chemical/p38 Mitogen-Activated Protein...,
http://linkedlifedata.com/resource/pubmed/chemical/rac GTP-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/rac2 GTP-binding protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Dec
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| pubmed:issn |
1440-1681
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| pubmed:author | |
| pubmed:copyrightInfo |
© 2010 The Authors. Clinical and Experimental Pharmacology and Physiology © 2010 Blackwell Publishing Asia Pty Ltd.
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| pubmed:issnType |
Electronic
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| pubmed:volume |
37
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
1147-53
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| pubmed:meshHeading |
pubmed-meshheading:20804509-Allyl Compounds,
pubmed-meshheading:20804509-Apoptosis,
pubmed-meshheading:20804509-Caspase 3,
pubmed-meshheading:20804509-Cell Line, Tumor,
pubmed-meshheading:20804509-DNA Fragmentation,
pubmed-meshheading:20804509-Disulfides,
pubmed-meshheading:20804509-Flow Cytometry,
pubmed-meshheading:20804509-HL-60 Cells,
pubmed-meshheading:20804509-Humans,
pubmed-meshheading:20804509-JNK Mitogen-Activated Protein Kinases,
pubmed-meshheading:20804509-Leukemia, Myeloid, Acute,
pubmed-meshheading:20804509-NADPH Oxidase,
pubmed-meshheading:20804509-Proto-Oncogene Proteins c-myc,
pubmed-meshheading:20804509-RNA, Small Interfering,
pubmed-meshheading:20804509-Reactive Oxygen Species,
pubmed-meshheading:20804509-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:20804509-Transcription Factor AP-1,
pubmed-meshheading:20804509-Up-Regulation,
pubmed-meshheading:20804509-p38 Mitogen-Activated Protein Kinases,
pubmed-meshheading:20804509-rac GTP-Binding Proteins
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| pubmed:year |
2010
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| pubmed:articleTitle |
Role of Ras-related C3 botulinum toxin substrate 2 (Rac2), NADPH oxidase and reactive oxygen species in diallyl disulphide-induced apoptosis of human leukaemia HL-60 cells.
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| pubmed:affiliation |
Cancer Research Institute, University of South China, Hengyang, Hunan Province, China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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