The role of glutathione in the regulation of nucleotide excision repair during oxidative stress.

2.50
Hdl Handle:
http://hdl.handle.net/10146/25432
Title:
The role of glutathione in the regulation of nucleotide excision repair during oxidative stress.
Authors:
Langie, Sabine A.S.; Knaapen, Ad M.; Houben, Joyce M.J.; van Kempen, Frederik C.; de Hoon, Joep P.J.; Gottschalk, Ralph W.H.; Godschalk, Roger W.L.; van Schooten, Frederik J.
Abstract:
Nucleotide excision repair (NER) mainly repairs bulky DNA adducts and helix distorting lesions, but is additionally considered to be a back-up system for base excision repair to remove oxidative stress induced DNA damage. Therefore, it can be speculated that NER is up-regulated or primed by oxidative stress. Exposure of human pulmonary epithelial cells (A549) to non-toxic doses of 100muM H(2)O(2) indeed showed a 2 to 4.5-fold increase in expression of XPA, XPC, ERCC4, and ERCC5, whereas the expression of ERCC1 was 5-fold decreased. Phenotypical assessment of NER capacity (i.e. recognition and incision of benzo[a]pyrene-DNA adducts) showed a significant decrease to less than 50% after H(2)O(2) exposure, which paralleled the effects of H(2)O(2) on ERCC1 expression. To study the possible involvement of glutathione (GSH) in the regulation of NER, cells were pre-incubated with 0.5mM BSO, resulting in total GSH depletion and increased intracellular oxidative stress. In GSH-depleted cells, the down-regulation of ERCC1 expression by H(2)O(2) was completely abolished and the up-regulation of ERCC4 expression was potentiated from 2.5-fold to >10-fold. Similarly, the H(2)O(2)-induced decrease in NER capacity was absent in GSH-depleted cells. Overall, our data suggest that NER capacity as well as the expression of NER related genes can be modulated by oxidative stress. ERCC1 expression and NER capacity correlated strongly (R(2)=0.85, P<0.01) after oxidant exposure, indicating ERCC1 as a specific target for oxidative stress induced modification of NER.
Citation:
Toxicol. Lett. 2007, 168 (3):302-309
Journal:
Toxicology Letters
Issue Date:
5-Feb-2007
URI:
http://hdl.handle.net/10146/25432
DOI:
10.1016/j.toxlet.2006.10.027
PubMed ID:
17207589
Additional Links:
http://ciah.pl/7450; http://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4MC12JG-D&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=7f861ead0245a7179f82cad9c62e0e5d
Type:
Article
Language:
en
ISSN:
0378-4274
Sponsors:
This work was supported by the European network of excellence ECNIS (FOOD-CT-2005-513943) on Environmental Cancer Risk, Nutrition and Individual Susceptibility. Ad M. Knaapen is supported by a postdoctoral fellowship from the Netherlands Organisation for Scientific Research (NWO, VENI-916.46.092).
Appears in Collections:
Articles

Full metadata record

DC FieldValue Language
dc.contributor.authorLangie, Sabine A.S.-
dc.contributor.authorKnaapen, Ad M.-
dc.contributor.authorHouben, Joyce M.J.-
dc.contributor.authorvan Kempen, Frederik C.-
dc.contributor.authorde Hoon, Joep P.J.-
dc.contributor.authorGottschalk, Ralph W.H.-
dc.contributor.authorGodschalk, Roger W.L.-
dc.contributor.authorvan Schooten, Frederik J.-
dc.date.accessioned2008-05-12T08:03:13Z-
dc.date.available2008-05-12T08:03:13Z-
dc.date.issued2007-02-05-
dc.identifier.citationToxicol. Lett. 2007, 168 (3):302-309en
dc.identifier.issn0378-4274-
dc.identifier.pmid17207589-
dc.identifier.doi10.1016/j.toxlet.2006.10.027-
dc.identifier.urihttp://hdl.handle.net/10146/25432-
dc.description.abstractNucleotide excision repair (NER) mainly repairs bulky DNA adducts and helix distorting lesions, but is additionally considered to be a back-up system for base excision repair to remove oxidative stress induced DNA damage. Therefore, it can be speculated that NER is up-regulated or primed by oxidative stress. Exposure of human pulmonary epithelial cells (A549) to non-toxic doses of 100muM H(2)O(2) indeed showed a 2 to 4.5-fold increase in expression of XPA, XPC, ERCC4, and ERCC5, whereas the expression of ERCC1 was 5-fold decreased. Phenotypical assessment of NER capacity (i.e. recognition and incision of benzo[a]pyrene-DNA adducts) showed a significant decrease to less than 50% after H(2)O(2) exposure, which paralleled the effects of H(2)O(2) on ERCC1 expression. To study the possible involvement of glutathione (GSH) in the regulation of NER, cells were pre-incubated with 0.5mM BSO, resulting in total GSH depletion and increased intracellular oxidative stress. In GSH-depleted cells, the down-regulation of ERCC1 expression by H(2)O(2) was completely abolished and the up-regulation of ERCC4 expression was potentiated from 2.5-fold to >10-fold. Similarly, the H(2)O(2)-induced decrease in NER capacity was absent in GSH-depleted cells. Overall, our data suggest that NER capacity as well as the expression of NER related genes can be modulated by oxidative stress. ERCC1 expression and NER capacity correlated strongly (R(2)=0.85, P<0.01) after oxidant exposure, indicating ERCC1 as a specific target for oxidative stress induced modification of NER.en
dc.description.sponsorshipThis work was supported by the European network of excellence ECNIS (FOOD-CT-2005-513943) on Environmental Cancer Risk, Nutrition and Individual Susceptibility. Ad M. Knaapen is supported by a postdoctoral fellowship from the Netherlands Organisation for Scientific Research (NWO, VENI-916.46.092).en
dc.language.isoenen
dc.relation.urlhttp://ciah.pl/7450en
dc.relation.urlhttp://www.sciencedirect.com/science?_ob=ArticleURL&_udi=B6TCR-4MC12JG-D&_user=1843694&_rdoc=1&_fmt=&_orig=search&_sort=d&view=c&_acct=C000055040&_version=1&_urlVersion=0&_userid=1843694&md5=7f861ead0245a7179f82cad9c62e0e5den
dc.subjectOxidative stressen
dc.subjectNucleotide excision repairen
dc.subjectDNA repair capacityen
dc.subjectGlutathioneen
dc.subject.meshButhionine Sulfoximine-
dc.subject.meshCell Line, Tumor-
dc.subject.meshDNA Repair-
dc.subject.meshDNA-Binding Proteins-
dc.subject.meshEndonucleases-
dc.subject.meshGene Expression Profiling-
dc.subject.meshGlutathione-
dc.subject.meshHumans-
dc.subject.meshHydrogen Peroxide-
dc.subject.meshOxidants-
dc.subject.meshOxidative Stress-
dc.subject.meshReverse Transcriptase Polymerase Chain Reaction-
dc.titleThe role of glutathione in the regulation of nucleotide excision repair during oxidative stress.en
dc.typeArticleen
dc.identifier.journalToxicology Lettersen

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