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001-es BibID:	BIBFORM051534
035-os BibID:	(Scopus)84896538802 (WoS)000332701400043
Első szerző:	Ba, Xueqing
Cím:	8-oxoguanine DNA glycosylase-1 augments proinflammatory gene expression by facilitating the recruitment of site-specific transcription factors / Xueqing Ba, Attila Bacsi, Jixian Luo, Leopoldo Aguilera-Aguirre, Xianlu Zeng, Zsolt Radak, Allan R. Brasier, Istvan Boldogh
Dátum:	2014
ISSN:	0022-1767 1550-6606
Megjegyzések:	Among the insidious DNA base lesions, 8-oxo-7,8-dihydroguanine (8-oxoG) is one of the most abundant, a lesion that arises through the attack by reactive oxygen species on guanine, especially when located in cis-regulatory elements. 8-oxoG is repaired by the 8-oxoguanine glycosylase 1 (OGG1)-initiated DNA base excision repair pathway. In this study, we investigated whether 8-oxoG repair by OGG1 in promoter regions is compatible with a prompt gene expression and a host innate immune response. For this purpose, we used a mouse model of airway inflammation, supplemented with cell cultures, chromatin immunoprecipitation, small interfering RNA knockdown, real-time PCR, and comet and reporter transcription assays. Our data show that exposure of cells to TNF-? altered cellular redox, increased the 8-oxoG level in DNA, recruited OGG1 to promoter sequences, and transiently inhibited base excision repair of 8-oxoG. Promoter-associated OGG1 then enhanced NF-?B/RelA binding to cis-elements and facilitated recruitment of specificity protein 1, transcription initiation factor II-D, and p-RNA polymerase II, resulting in the rapid expression of chemokines/cytokines and inflammatory cell accumulation in mouse airways. Small interfering RNA depletion of OGG1 or prevention of guanine oxidation significantly decreased TNF-?-induced inflammatory responses. Taken together, these results show that nonproductive binding of OGG1 to 8-oxoG in promoter sequences could be an epigenetic mechanism to modulate gene expression for a prompt innate immune response.
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban folyóiratcikk OGG1 8-oxoG trans-ACTING FACTORS INNATE IMMUNE RESPONSE
Megjelenés:	Journal of Immunology. - 192 : 5 (2014), p. 2384-2394. -
További szerzők:	Bácsi Attila (1967-) (immunológus) Luo, Jixian Aguilera-Aguirre, Leopoldo Zeng, Xianlu Radák Zsolt Brasier, Allan R. Boldogh István
Pályázati támogatás:	4.2.2.A-11/1/KONV-2012-0023 TÁMOP
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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001-es BibID:	BIBFORM055557
Első szerző:	Luo, Jixian
Cím:	8-Oxoguanine DNA glycosylase-1-mediated DNA repair is associated with Rho GTPase activation and α-smooth muscle actin polymerization / Jixian Luo, Koa Hosoki, Attila Bacsi, Zsolt Radak, Muralidhar L. Hegde, Sanjiv Sur, Tapas K. Hazra, Allan R. Brasier, Xueqing Ba, Istvan Boldogh
Dátum:	2014
ISSN:	0891-5849
Megjegyzések:	Reactive oxygen species (ROS) are activators of cell signaling and modify cellular molecules, including DNA. 8-Oxo-7,8-dihydroguanine (8-oxoG) is one of the prominent lesions in oxidatively damaged DNA, whose accumulation is causally linked to various diseases and aging processes, whereas its etiological relevance is unclear. 8-OxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair (BER) pathway. OGG1 binds free 8-oxoG and this complex functions as an activator of Ras family GTPases. Here we examined whether OGG1-initiated BER is associated with the activation of Rho GTPase and mediates changes in the cytoskeleton. To test this possibility, we induced OGG1-initiated BER in cultured cells and mouse lungs and used molecular approaches such as active Rho pull-down assays, siRNA ablation of gene expression, immune blotting, and microscopic imaging. We found that OGG1 physically interacts with Rho GTPase and, in the presence of 8-oxoG base, increases Rho-GTP levels in cultured cells and lungs, which mediates ?-smooth muscle actin (?-SMA) polymerization into stress fibers and increases the level of ?-SMA in insoluble cellular/tissue fractions. These changes were absent in cells lacking OGG1. These unexpected data and those showing that 8-oxoG repair is a lifetime process suggest that, via Rho GTPase, OGG1 could be involved in the cytoskeletal changes and organ remodeling observed in various chronic diseases.
Tárgyszavak:	Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:	Free Radical Biology and Medicine. - 73 (2014), p. 430-438. -
További szerzők:	Hosoki, Koa Bácsi Attila (1967-) (immunológus) Radák Zsolt Hegde, Muralidhar L. Sur, Sanjiv Hazra, Tapas K. Brasier, Allan R. Ba, Xueqing Boldogh István
Internet cím:	Szerző által megadott URL DOI Intézményi repozitóriumban (DEA) tárolt változat
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