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001-es BibID:BIBFORM047651
Első szerző:Hajas György (biológus)
Cím:8-Oxoguanine DNA glycosylase-1 links DNA repair to cellular signaling via the activation of the small GTPase Rac1 / Gyorgy Hajas, Attila Bacsi, Leopoldo Aguilera-Aguirre, Muralidhar L. Hegde, K. Hazra Tapas, Sanjiv Sur, Zsolt Radak, Xueqing Ba, Istvan Boldogh
Dátum:2013
ISSN:0891-5849
Megjegyzések:8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the most abundant DNA base lesions induced by reactive oxygen species (ROS). Accumulation of 8-oxoG in the mammalian genome is considered a marker of oxidative stress, to be causally linked to inflammation, and is thought to contribute to aging processes and various aging-related diseases. Unexpectedly, mice that lack 8-oxoguanine DNA glycosylase-1 (OGG1) activity and accumulate 8-oxoG in their genome have a normal phenotype and longevity; in fact, they show increased resistance to both inflammation and oxidative stress. OGG1 excises and generates free 8-oxoG base during DNA base-excision repair (BER) processes. In the present study, we report that in the presence of the 8-oxoG base, OGG1 physically interacts with guanine nucleotide-free and GDP-bound Rac1 protein. This interaction results in rapid GDP?GTP, but not GTP?GDP, exchange in vitro. Importantly, a rise in the intracellular 8-oxoG base levels increases the proportion of GTP-bound Rac1. In turn Rac1-GTP mediates an increase in ROS levels via nuclear membrane-associated NADPH oxidase type 4. These results show a novel mechanism by which OGG1 in complex with 8-oxoG is linked to redox signaling and cellular responses.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
8-Oxoguanine DNA glycosylase-1
8-Oxoguanine
Rac1 GTPase
Megjelenés:Free Radical Biology And Medicine. - 61C (2013), p. 384-394. -
További szerzők:Bácsi Attila (1967-) (immunológus) Aguilera-Aguirre, Leopoldo Hegde, Muralidhar L. Tapas, K. Hazra Sur, Sanjiv Radák Zsolt Ba, Xueqing Boldogh István
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001-es BibID:BIBFORM030561
Első szerző:Hajas György (biológus)
Cím:Biochemical identification of a hydroperoxide derivative of the free 8-oxo-7,8-dihydroguanine base / Gyorgy Hajas, Attila Bacsi, Leopoldo Aguilerra-Aguirre, Peter German, Zsolt Radak, Sanjiv Sur, Tapas K. Hazra, Istvan Boldogh
Dátum:2012
ISSN:0891-5849
Megjegyzések:-Oxo-7,8-dihydroguanine is one the most abundant base lesions in pro- and eukaryotic DNA. In mammalian cells, it is excised by the 8-oxoguanine DNA glycosylase (OGG1) during DNA base-excision repair, and the generated free 8-oxoG base is one of the DNA-derived biomarkers of oxidative stress in biological samples. The modification of 8-oxoG in the context of nucleoside and DNA has been the subject of many studies; however, the oxidative transformation of the free 8-oxoG base has not been described. By using biochemical and cell biological assays, we show that in the presence of molecular oxygen, the free 8-oxoG base transforms to a highly reactive hydroperoxide (8-oxoG*). Specifically, 8-oxoG* oxidizes Amplex red to resorufin, H(2)DCF to DCF, Fe(2+) to Fe(3+), and GSH to GSSG. This property of 8-oxoG* was diminished by treatment with catalase and glutathione peroxidase, but not superoxide dismutase. 8-OxoG* formation was prevented by reducing agents or nitrogen atmosphere. Its addition to CM-H(2)DCF-DA-loaded cells rapidly increased intracellular DCF fluorescence. There were no such properties observed for 8-oxodeoxyguanosine, 2,6-diamino-4-hydroxy-5-formamidopyrimidine, 2'-deoxyguanosine, guanine, adenine, guanosine, and 8-hydroxyadenine. These data imply that a free 8-oxoG base is more susceptible to oxidation than is its nucleoside form and, consequently, it stands as unique among intact and oxidatively modified purines.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Molekuláris Medicina
Free 8-oxoguanine base
Oxidative stress
Free radicals
külföldön készült közlemény
Megjelenés:Free Radical Biology And Medicine 52 : 4 (2012), p. 749-756. -
További szerzők:Bácsi Attila (1967-) (immunológus) Aguilera-Aguirre, Leopoldo Germán Péter (gyermekgyógyász) Radák Zsolt Sur, Sanjiv Hazra, Tapas K. Boldogh István
Pályázati támogatás:TÁMOP-4.2.1/B-09/1/KONV-2010-0007
TÁMOP
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DOI
Intézményi repozitóriumban (DEA) tárolt változat
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