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001-es BibID:BIBFORM065564
Első szerző:Aguilera-Aguirre, Leopoldo
Cím:Whole transcriptome analysis reveals a role for OGG1-initiated DNA repair signaling in airway remodeling / Leopoldo Aguilera-Aguirre, Koa Hosoki, Attila Bacsi, Zsolt Radák, Sanjiv Sur, Muralidhar L. Hegde, Bing Tian, Alfredo Saavedra-Molina, Allan R. Brasier, Xueqing Ba, Istvan Boldogh
Dátum:2015
ISSN:0891-5849
Megjegyzések:Reactive oxygen species (ROS) generated by environmental exposures, and endogenously as by-products of respiration, oxidatively modify biomolecules including DNA. Accumulation of ROS-induced DNA damage has been implicated in various diseases that involve inflammatory processes, and efficient DNA repair is considered critical in preventing such diseases. One of the most abundant DNA base lesions is 7,8-dihydro-8-oxoguanine (8-oxoG), which is repaired by the 8-oxoguanine DNA glycosylase 1 (OGG1)-initiated base-excision repair (OGG1-BER) pathway. Recent studies have shown that the OGG1-BER by-product 8-oxoG base forms a complex with cytosolic OGG1, activating small GTPases and downstream cell signaling in cultured cells and lungs. This implies that persistent OGG1-BER could result in signaling leading to histological changes in airways. To test this, we mimicked OGG1-BER by repeatedly challenging airways with its repair product 8-oxoG base. Gene expression was analyzed by RNA sequencing (RNA-Seq) and qRT-PCR, and datasets were evaluated by gene ontology and statistical tools. RNA-Seq analysis identified 3252 differentially expressed transcripts (2435 up- and 817 downregulated, ? 3-fold change). Among the upregulated transcripts, 2080 mRNAs were identified whose encoded protein products were involved in modulation of the actin family cytoskeleton, extracellular matrix, cell adhesion, cadherin, and cell junctions, affecting biological processes such as tissue development, cell-to-cell adhesion, cell communication, and the immune system. These data are supported by histological observations showing epithelial alterations, subepithelial fibrosis, and collagen deposits in the lungs. These data imply that continuous challenge by the environment and consequent OGG1-BER-driven signaling trigger gene expression consistent with airway remodeling.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
8-Oxoguanine
Airway remodeling
OGG1-BER
Megjelenés:Free Radical Biology And Medicine 89 (2015), p. 20-33. -
További szerzők:Hosoki, Koa Bácsi Attila (1967-) (immunológus) Radák Zsolt Sur, Sanjiv Hegde, Muralidhar L. Tian, Bing Saavedra-Molina, Alfredo Brasier, Allan R. Ba, Xueqing Boldogh István
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2.

001-es BibID:BIBFORM065605
Első szerző:Aguilera-Aguirre, Leopoldo
Cím:Whole transcriptome analysis reveals an 8-oxoguanine DNA glycosylase-1-driven DNA repair-dependent gene expression linked to essential biological processes / Leopoldo Aguilera-Aguirre, Koa Hosoki, Attila Bacsi, Zsolt Radák, Thomas G. Wood, Steven G. Widen, Sanjiv Sur, Bill T. Ameredes, Alfredo Saavedra-Molina, Allan R. Brasier, Xueqing Ba, Istvan Boldogh
Dátum:2015
ISSN:0891-5849
Megjegyzések:Reactiveoxygenspeciesinflict oxidativemodifications onvariousbiologicalmolecules,includingDNA.One ofthemostabundantDNAbaselesions,8-oxo-7,8-dihydroguanine(8-oxoG)isrepairedby8-oxoguanineDNAglycosylase-1(OGG1)duringDNAbaseexcisionrepair(OGG1-BER).8-OxoGaccumula-tion inDNAhasbeenassociatedwithvariouspathologicalandagingprocesses,althoughitsroleisunclear.ThelackofOGG1-BERin Ogg1 / mice resultedindecreasedinflammatory responsesandincreased susceptibilitytoinfectionsandmetabolicdisorders.Therefore,weproposedthatOGG1and/or8-oxoGbasemayhavearoleinimmuneandhomeostaticprocesses.Totestourhypothesis,wechallenged mouselungswithOGG1-BERproduct8-oxoGbaseandchangesingeneexpressionweredetermined byRNAsequencinganddatawereanalyzedbyGeneOntologyandstatisticaltools.RNA-Seqanalysisidentified 1592differentiallyexpressed(Z 3-fold change)transcripts.TheupregulatedmRNAswererelatedtobiologicalprocesses,includinghomeostatic,immune-system,macrophageactivation,regulation ofliquid-surfacetension,andresponsetostimulus.Theseprocessesweremediatedbychemokines, cytokines,gonadotropin-releasinghormonereceptor,integrin,andinterleukinsignalingpathways.Takentogether,these findings pointtoanewparadigmshowingthatOGG1-BERplaysarolein variousbiologicalprocessesthatmaybenefit thehost,butwheninexcesscouldbeimplicatedindisease and/oragingprocesses.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
OGG1-BER
8-Oxoguanine
Gene expression
Biological processes
Megjelenés:Free Radical Biology And Medicine. - 81 (2015), p. 107-118. -
További szerzők:Hosoki, Koa Bácsi Attila (1967-) (immunológus) Radák Zsolt Wood, Thomas G. Widen, Steven G. Sur, Sanjiv Ameredes, Bill T. Saavedra-Molina, Alfredo Brasier, Allan R. Ba, Xueqing Boldogh István
Pályázati támogatás:TAMOP4.2.2.A-11/1/KONV- 2012?2023
Egyéb
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3.

001-es BibID:BIBFORM055556
035-os BibID:(scopus)84907867357 (wos)000343109700119
Első szerző:Ba, Xueqing
Cím:The Role of 8-Oxoguanine DNA Glycosylase-1 in Inflammation / Xueqing Ba, Leopoldo Aguilera-Aguirre, Qura Tul Ain Nmi Rashid, Attila Bacsi, Zsolt Radak, Sanjiv Sur, Koa Hosoki, Muralidhar L. Hegde, Istvan Boldogh
Dátum:2014
ISSN:1661-6596 1422-0067
Megjegyzések:Many, if not all, environmental pollutants/chemicals and infectious agents increase intracellular levels of reactive oxygen species (ROS) at the site of exposure. ROS not only function as intracellular signaling entities, but also induce damage to cellular molecules including DNA. Among the several dozen ROS-induced DNA base lesions generated in the genome, 8-oxo-7,8-dihydroguanine (8-oxoG) is one of the most abundant because of guanine's lowest redox potential among DNA bases. In mammalian cells, 8-oxoG is repaired by the 8-oxoguanine DNA glycosylase-1 (OGG1)-initiated DNA base excision repair pathway (OGG1-BER). Accumulation of 8-oxoG in DNA has traditionally been associated with mutagenesis, as well as various human diseases and aging processes, while the free 8-oxoG base in body fluids is one of the best biomarkers of ongoing pathophysiological processes. In this review, we discuss the biological significance of the 8-oxoG base and particularly the role of OGG1-BER in the activation of small GTPases and changes in gene expression, including those that regulate pro-inflammatory chemokines/cytokines and cause inflammation.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:International Journal of Molecular Sciences. - 15 : 9 (2014), p. 16975-16997. -
További szerzők:Aguilera-Aguirre, Leopoldo Rashid, Qura Tul Ain Nmi Bácsi Attila (1967-) (immunológus) Radák Zsolt Sur, Sanjiv Hosoki, Koa Hegde, Muralidhar L. Boldogh István
Pályázati támogatás:TAMOP 4.2.2.A-11/1/KONV-2012-2023
TÁMOP
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4.

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
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