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001-es BibID:	BIBFORM041838
Első szerző:	Bácsi Attila (immunológus)
Cím:	Down-regulation of 8-oxoguanine DNA glycosylase 1 expression in the airway epithelium ameliorates allergic lung inflammation / Bacsi Attila, Aguilera-Aguirre Leopoldo, Szczesny Bartosz, Radak Zsolt, Hazra Tapas K., Sur Sanjiv, Ba Xueqing, Boldogh Istvan
Dátum:	2013
ISSN:	1568-7864
Megjegyzések:	Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston Allergic airway inflammation is characterized by increased expression of pro-inflammatory mediators, inflammatory cell infiltration, mucus hypersecretion, and airway hyperresponsiveness, in parallel with oxidative DNA base and strand damage, whose etiological role is not understood. Our goal was to establish the role of 8-oxoguanine (8-oxoG), a common oxidatively damaged base, and its repair by 8-oxoguanine DNA glycosylase 1 (Ogg1) in allergic airway inflammatory processes. Airway inflammation was induced by intranasally administered ragweed (Ambrosia artemisiifolia) pollen grain extract (RWPE) in sensitized BALB/c mice. We utilized siRNA technology to deplete Ogg1 from airway epithelium; 8-oxoG and DNA strand break levels were quantified by Comet assays. Inflammatory cell infiltration and epithelial methaplasia were determined histologically, mucus and cytokines levels biochemically and enhanced pause was used as the main index of airway hyperresponsiveness. Decreased Ogg1 expression and thereby 8-oxoG repair in the airway epithelium conveyed a lower inflammatory response after RWPE challenge of sensitized mice, as determined by expression of Th2 cytokines, eosinophilia, epithelial methaplasia, and airway hyperresponsiveness. In contrast, 8-oxoG repair in Ogg1-proficient airway epithelium was coupled to an increase in DNA single-strand break (SSB) levels and exacerbation of allergen challenge-dependent inflammation. Decreased expression of the Nei-like glycosylases Neil1 and Neil2 that preferentially excise ring-opened purines and 5-hydroxyuracil, respectively, did not alter the above parameters of allergic immune responses to RWPE. These results show that DNA SSBs formed during Ogg1-mediated repair of 8-oxoG augment antigen-driven allergic immune responses. A transient modulation of OGG1 expression/activity in airway epithelial cells could have clinical benefits.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Allergic inflammation DNA repair Oxidative DNA damage Oxidative stress 8-Oxoguanine 8-Oxoguanine DNA glycosylase 1 Molekuláris Medicina
Megjelenés:	Dna Repair. - 12 : 1 (2013), p. 18-26. -
További szerzők:	Aguilera-Aguirre, Leopoldo Szczesny, Bartosz Radák Zsolt Hazra, Tapas K. Sur, Sanjiv Ba, Xueqing Boldogh István
Pályázati támogatás:	TÁMOP-4.2.1/B-09/1/KONV-2010-0007 TÁMOP Az oxidatív DNS károsodások javítása és a gyulladás kialakulásának kapcsolata
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001-es BibID:	BIBFORM047640
Első szerző:	Germán Péter (gyermekgyógyász)
Cím:	Activation of cellular signaling by 8-oxoguanine DNA glycosylase-1-initiated DNA base excision repair / Peter German, Peter Szaniszlo, Gyorgy Hajas, Zsolt Radak, Attila Bacsi, Tapas K. Hazra, Muralidhar L. Hegde, Xueqing Ba, Istvan Boldogh
Dátum:	2013
ISSN:	1568-7864
Megjegyzések:	Accumulation of 8-oxo-7,8-dihydroguanine (8-oxoG) in the DNA results in genetic instability and mutagenesis, and is believed to contribute to carcinogenesis, aging processes and various aging-related diseases. 8-OxoG is removed from the DNA via DNA base excision repair (BER), initiated by 8-oxoguanine DNA glycosylase-1 (OGG1). Our recent studies have shown that OGG1 binds its repair product 8-oxoG base with high affinity at a site independent from its DNA lesion-recognizing catalytic site and the OGG1?8-oxoG complex physically interacts with canonical Ras family members. Furthermore, exogenously added 8-oxoG base enters the cells and activates Ras GTPases; however, a link has not yet been established between cell signaling and DNA BER, which is the endogenous source of the 8-oxoG base. In this study, we utilized KG-1 cells expressing a temperature-sensitive mutant OGG1, siRNA ablation of gene expression, and a variety of molecular biological assays to define a link between OGG1-BER and cellular signaling. The results show that due to activation of OGG1-BER, 8-oxoG base is released from the genome in sufficient quantities for activation of Ras GTPase and resulting in phosphorylation of the downstream Ras targets Raf1, MEK1,2 and ERK1,2. These results demonstrate a previously unrecognized mechanism for cellular responses to OGG1-initiated DNA BER.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Ogg1 Base excision repair Cell signaling
Megjelenés:	Dna Repair. - 12 : 10 (2013), p. 856-863. -
További szerzők:	Szaniszló Péter Hajas György (1970-) (biológus) Radák Zsolt Bácsi Attila (1967-) (immunológus) Hazra, Tapas K. Hegde, Muralidhar L. Ba, Xueqing Boldogh István
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