Source:http://linkedlifedata.com/resource/pubmed/id/12708745
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| Predicate | Object |
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| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
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| pubmed:dateCreated |
2003-4-23
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| pubmed:abstractText |
Recently Hippophae rhamnoides has been reported to render chromatin compaction and significantly inhibit radiation induced DNA strand breaks. To investigate the mechanism of action of RH-3, a preparation of Hippophae rhamnoides, in this connection, present study was undertaken. Chromatin compaction induced by RH-3 (100 microg/ml or more) was maximum at alkaline pH but was completely negated by acidic pH (< 6) or presence of free radical scavengers like glycerol, DMSO etc. In a concentration dependent manner, RH-3 inhibited the intercalation of ethidium ions from Et Br into calf thymus DNA and also increased the precipitation of DNA-protein cross-links (DPC) in thymocytes. Chromatin compaction caused by RH-3 treatment did not permit the separation of proteins from DNA even after treatment with 2 M NaCl solution. SDS-PAGE profiles also revealed that RH-3 in a dose dependent manner compacted the chromatin organization, induced DPC and inhibited the extraction of both histone and non-histone matrix proteins from chromatin maximally at 80 microg/ml. More than 80 microg/ml of RH-3, though extracted low molecular weight histones but did not separate non-histone proteins. The RH-3 mediated DPCs were resistant even to 1% SDS, 4 M NaCl and 3.8 M hydroxyl amine hydrochloride but were prone to both urea (8 M) and guanidine hydrochloride (6 M) indicating covalent bonding between DNA and proteins (serine/threonine). RH-3 in a concentration dependent manner induced superoxide anions and the phenomenon was dependent upon nature of medium, presence of metal ions and pH. RH-3 at concentrations up to 100 microg/ml in presence of 50 microM copper sulfate inflicted significant damage to extraneously added 2-deoxyribose molecules and maximum TBARS were formed at a concentration of 100 microg/ml. Higher concentrations of RH-3 more than 100 microg/ml quenched free radicals and inhibited 2-deoxyribose degradation. RH-3 also induced strand breaks in plasmid DNA at concentrations lower than 100 microg/ml but completely inhibited at concentrations higher than 250 microg/ml, indicating bimodal function. Strand breaks induced by lower concentrations of RH-3 (up to 100 microg/ml) were inhibited by antioxidants like GSH, DFR etc. RH-3, in a concentration dependent mode also inhibited the relaxation of supercoiled plasmid DNA (PBR322) by topoisomerase I. Present study indicated that RH-3 caused compaction of reversible (< 100 micrpg/ml) and irreversible (> 100 microg/ml) nature which was related to the magnitude of DNA-protein cross-links formed. Maintenance of chromatin organization, induction of hypoxia, hydrogen atom donation, free radical scavenging and blocking of cell cycle at G2-M phase by interfering with topoisomerase I activity seem to contribute towards the radioprotective efficacy of RH-3.
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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/Antioxidants,
http://linkedlifedata.com/resource/pubmed/chemical/Chromatin,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/DNA,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Topoisomerases, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Free Radical Scavengers,
http://linkedlifedata.com/resource/pubmed/chemical/Hydroxyl Radical,
http://linkedlifedata.com/resource/pubmed/chemical/Plant Extracts,
http://linkedlifedata.com/resource/pubmed/chemical/Radiation-Protective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Thiobarbituric Acid Reactive...,
http://linkedlifedata.com/resource/pubmed/chemical/Topoisomerase I Inhibitors
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| pubmed:status |
MEDLINE
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| pubmed:month |
Mar
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| pubmed:issn |
0300-8177
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:volume |
245
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
57-67
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| pubmed:dateRevised |
2010-11-18
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| pubmed:meshHeading |
pubmed-meshheading:12708745-Animals,
pubmed-meshheading:12708745-Antioxidants,
pubmed-meshheading:12708745-Cell Hypoxia,
pubmed-meshheading:12708745-Cells, Cultured,
pubmed-meshheading:12708745-Chromatin,
pubmed-meshheading:12708745-Cross-Linking Reagents,
pubmed-meshheading:12708745-DNA,
pubmed-meshheading:12708745-DNA Damage,
pubmed-meshheading:12708745-DNA Topoisomerases, Type I,
pubmed-meshheading:12708745-Dose-Response Relationship, Drug,
pubmed-meshheading:12708745-Free Radical Scavengers,
pubmed-meshheading:12708745-Gamma Rays,
pubmed-meshheading:12708745-Hippophae,
pubmed-meshheading:12708745-Hydrogen-Ion Concentration,
pubmed-meshheading:12708745-Hydroxyl Radical,
pubmed-meshheading:12708745-Male,
pubmed-meshheading:12708745-Mice,
pubmed-meshheading:12708745-Mice, Inbred A,
pubmed-meshheading:12708745-Plant Extracts,
pubmed-meshheading:12708745-Radiation-Protective Agents,
pubmed-meshheading:12708745-Thiobarbituric Acid Reactive Substances,
pubmed-meshheading:12708745-Thymus Gland,
pubmed-meshheading:12708745-Topoisomerase I Inhibitors
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| pubmed:year |
2003
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| pubmed:articleTitle |
Induction of DNA-protein cross-links by Hippophae rhamnoides: implications in radioprotection and cytotoxicity.
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| pubmed:affiliation |
Department of Radiation Biology, Institute of Nuclear Medicine and Allied Sciences, Brig S.K. Majumdar Marg, Delhi, India. radbiol@nda.vsnl.net.in
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| pubmed:publicationType |
Journal Article
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