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1.

001-es BibID:BIBFORM072833
Első szerző:Aguilera-Aguirre, Leopoldo
Cím:Pollen-induced oxidative DNA damage response regulates miRNAs controlling allergic inflammation / Aguilera-Aguirre Leopoldo, Hao Wenging, Pan Lang, Li Xiaoxue, Saavedra-Molina Alfredo, Bacsi Attila, Radak Zsolt, Sur Sanjiv, Brasier Allan R., Ba Xueqing, Boldogh Istvan
Dátum:2017
ISSN:1040-0605 1522-1504
Megjegyzések:A mucosal oxidative burst is a hallmark response to pollen exposure that promotes allergic inflammatory responses. Reactive species constituents of oxidative stress signal via the modification of cellular molecules including nucleic acids. One of the most abundant forms of oxidative genomic base damage is 8-oxo-7,8-dihydroguanine (8-oxoG), which is removed from DNA by 8-oxoguanine DNA glycosylase 1 (OGG1). OGG1 in complex with 8-oxoG acts as a GDP-GTP exchange factor and induces acute inflammation; however, the mechanism(s) by which OGG1 signaling regulates allergic airway inflammation is not known. Here, we postulate that the OGG1 signaling pathway differentially altered the levels of small regulatory RNAs and increased the expression of T helper 2 (Th2) cytokines in ragweed pollen extract (RWPE)-challenged lungs. To determine this, the lungs of sensitized mice expressing or lacking OGG1 were challenged with RWPE and/or with OGG1's excision product 8-oxoG. The responses in lungs were assessed by next-generation sequencing, as well as various molecular and histological approaches. The results showed that RWPE challenge induced oxidative burst and damage to DNA and activated OGG1 signaling, resulting in the differential expression of 84 micro-RNAs (miRNAs), which then exacerbated antigen-driven allergic inflammation and histological changes in the lungs. The exogenous administration of the downregulated let-7b-p3 mimetic or inhibitors of upregulated miR-23a or miR-27a decreased eosinophil recruitment and mucus and collagen production via controlling the expression of IL-4, IL-5, and IL-13. Together, these data demonstrate the roles of OGG1 signaling in the regulation of antigen-driven allergic immune responses via differential expression of miRNAs upstream of Th2 cytokines and eosinophils.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
DNA repair
allergy
cell signaling
micro-RNAs
Megjelenés:American Journal Of Physiology-Lung Cellular And Molecular Physiology 313 : 6 (2017), p. L1058-L1068. -
További szerzők:Hao, Wenging Pan, Lang Li, Xiaoxue Saavedra-Molina, Alfredo Bácsi Attila (1967-) (immunológus) Radák Zsolt Sur, Sanjiv Brasier, Allan R. Ba, Xueqing Boldogh István
Pályázati támogatás:OTKA-109595
OTKA
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2.

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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3.

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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4.

001-es BibID:BIBFORM055555
Első szerző:Aguilera-Aguirre, Leopoldo
Cím:Innate Inflammation Induced by the 8-Oxoguanine DNA Glycosylase-1-KRAS-NF-kB Pathway / Leopoldo Aguilera-Aguirre, Attila Bacsi, Zsolt Radak, Tapas K. Hazra, Sankar Mitra, Sanjiv Sur, Allan R. Brasier, Xueqing Ba, Istvan Boldogh
Dátum:2014
ISSN:0022-1767 1550-6606
Megjegyzések:8-Oxoguanine-DNA glycosylase-1 (OGG1) is the primary enzyme for repairing 7,8-dihydro-8-oxoguanine (8-oxoG) via the DNAbase excision repair pathway (OGG1-BER). Accumulation of 8-oxoG in the genomic DNA leads to genetic instability and carcinogenesis and is thought to contribute to the worsening of various inflammatory and disease processes. However, the disease mechanism is unknown. In this study, we proposed that the mechanistic link between OGG1-BER and proinflammatory gene expression is OGG1's guanine nucleotide exchange factor activity, acquired after interaction with the 8-oxoG base and consequent activationof the small GTPase RAS. To test this hypothesis, we used BALB/c mice expressing or deficient in OGG1 in their airwayepithelium and various molecular biological approaches, including active RAS pulldown, reporter and Comet assays, small interfering RNA?mediated depletion of gene expression, quantitative RT-PCR, and immunoblotting. We report that the OGG1-intiated repair of oxidatively damaged DNA is a prerequisite for GDP?GTP exchange, KRAS-GTP?driven signaling via MAP kinases and PI3 kinases and mitogen-stress?related kinase-1 for NF-kB activation, proinflammatory chemokine/cytokine expression, and inflammatory cell recruitment to the airways. Mice deficient in OGG1-BER showed significantly decreasedimmune responses, whereas a lack of other Nei-like DNA glycosylases (i.e., NEIL1 and NEIL2) had no significant effect. These data unveil a previously unidentified role of OGG1-driven DNA BER in the generation of endogenous signals for inflammation in the innate signaling pathway.
Tárgyszavak:Természettudományok Biológiai tudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Immunology. - 193 : 9 (2014), p. 4643-4653. -
További szerzők:Bácsi Attila (1967-) (immunológus) Radák Zsolt Hazra, Tapas K. Mitra, Sankar Sur, Sanjiv Brasier, Allan R. Ba, Xueqing Boldogh István
Pályázati támogatás:TAMOP 4.2.2.A-11/1/KONV-2012-2023
TÁMOP
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5.

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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6.

001-es BibID:BIBFORM051534
035-os BibID: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
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
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7.

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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8.

001-es BibID:BIBFORM091749
Első szerző:Boldogh István
Cím:OGG1 at the Crossroads of Inflammation and DNA Base Excision Repair / I. Boldogh, L. Pan, S. Vlahopoulos, X. Zheng, K. Wang, T. K. Hazra, M. L. Hegde, A. Bacsi, Z. Radak, A. R. Brasier, X. Ba
Dátum:2020
Megjegyzések:Oxidative modification(s) to nucleic acid bases are an unavoidable consequence of reactions by reactive oxygen species. Arguably, the most abundant ROS-generated lesion in nuclear and mitochondrial DNA is 7, 8-dihydro-8-oxoguanine (8-oxoGua), which is repaired primarily by 8-oxoguanine DNA glycosylase 1, in the OGG1-initiated base excision repair pathway. Deficiency in OGG1 repair is believed to have role(s) in development and progression of various disease processes, including neurodegenerative, cardiovascular, metabolic diseases, and aging-associated pathologies. The common link among these diseases is acute/chronic inflammatory processes. Emerging data support the idea that OGG1-induced adjustments in DNA structure at genomic 8-oxoGua with or without excision, serve as a nucleation site for transcription factor binding allowing prompt expression of genes, essential for reestablishment of a homeostatic state via innate and adaptive immune responses after exposure to biological and/or cytotoxic agents. As part of the immune defenses, OGG1 in complex with a free 8-oxoGua base also exerts transcriptional control via small GTPase signaling pathways. These data are consistent with the limited immune responses of Ogg1 knockout mice. Thus, evolution integrated genome maintenance by OGG1-BER and control host homeostatic state via inflammation, which, if not controlled, can be one of the mechanistic explanations for OGG1's previously proposed link to diseases and aging processes.
ISBN:978-1-83916-251-0; 978-1-83916-254-1; 978-1-83916-256-5
Tárgyszavak:Természettudományok Biológiai tudományok könyvfejezet
könyvrészlet
OGG1
Megjelenés:DNA Damage, DNA Repair and Disease: Volume 2 / Eds. Miral Dizdaroglu, R. Stephen Lloyd. - p. 75-103. -
További szerzők:Pan, Lang Vlahopoulos, Spiros A. Zheng, Xiaoxiang Wang, K. Hazra, Tapas K. Hegde, Muralidhar L. Bácsi Attila (1967-) (immunológus) Radák Zsolt Brasier, Allan R. Ba, Xueqing
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9.

001-es BibID:BIBFORM041839
Első szerző:Boldogh István
Cím:Activation of ras signaling pathway by 8-oxoguanine DNA glycosylase bound to its excision product, 8-oxoguanine / Istvan Boldogh, Gyorgy Hajas, Leopoldo Aguilera-Aguirre, Muralidhar L. Hegde, Zsolt Radak, Attila Bacsi, Sanjiv Sur, Tapas K. Hazra, Sankar Mitra
Dátum:2012
ISSN:0021-9258
Megjegyzések:8-Oxo-7,8-dihydroguanine (8-oxoG), arguably the most abundant base lesion induced in mammalian genomes by reactive oxygen species, is repaired via the base excision repair pathway that is initiated with the excision of 8-oxoG by OGG1. Here we show that OGG1 binds the 8-oxoG base with high affinity and that the complex then interacts with canonical Ras family GTPases to catalyze replacement of GDP with GTP, thus serving as a guanine nuclear exchange factor. OGG1-mediated activation of Ras leads to phosphorylation of the mitogen-activated kinases MEK1,2/ERK1,2 and increasing downstream gene expression. These studies document for the first time that in addition to its role in repairing oxidized purines, OGG1 has an independent guanine nuclear exchange factor activity when bound to 8-oxoG.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
Megjelenés:Journal of Biological Chemistry 287 : 25 (2012), p. 20769-20773. -
További szerzők:Hajas György (1970-) (biológus) Aguilera-Aguirre, Leopoldo Hegde, Muralidhar L. Radák Zsolt Bácsi Attila (1967-) (immunológus) Sur, Sanjiv Hazra, Tapas K. Mitra, Sankar
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10.

001-es BibID:BIBFORM065562
Első szerző:Germán Péter (gyermekgyógyász)
Cím:8-Oxoguanine DNA glycosylase1-driven DNA repair : a paradoxical role in lung aging / Peter German, David Saenz, Peter Szaniszlo, Leopoldo Aguilera-Aguirre, Lang Pan, Muralidhar L. Hegde, Attila Bacsi, Gyorgy Hajas, Zsolt Radak, Xueqing Ba, Sankar Mitra, John Papaconstantinou, Istvan Boldogh
Dátum:2017
ISSN:0047-6374
Megjegyzések:Age-associated changes in lung structure and function are some of the most important predictors of overall health, cognitive activities and longevity. Common to all aging cells is an increase in oxidatively modified DNA bases, primarily 8-oxo-7,8-dihydroguanine (8-oxoG). It is repaired via DNA base excision repair pathway driven by 8-oxoguanine DNA glycosylase-1 (OGG1-BER), whose role in aging has been the focus of many studies. This study hypothesizes that signaling and consequent gene expression during cellular response to OGG1-BER "wires" senescence/aging processes. To test OGG1-BER was mimicked by repeatedly exposing diploid lung fibroblasts cells and airways of mice to 8-oxoG base. Results showed that repeated exposures led to G1 cell cycle arrest and pre-matured senescence of cultured cells in which over 1000 genes were differentially expressed -86% of them been identical to those in naturally senesced cells. Gene ontology analysis of gene expression displayed biological processes driven by small GTPases, phosphoinositide 3-kinase and mitogen activated kinase cascades both in cultured cells and lungs. These results together, points to a new paradigm about the role of DNA damage and repair by OGG1 in aging and age-associated disease processes.
Tárgyszavak:Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban
OGG1
8-oxoguanine
Senescence
Aging
Megjelenés:Mechanisms Of Ageing And Development 161 : Pt A (2017), p. 51-65. -
További szerzők:Saenz, David N. Szaniszló Péter Aguilera-Aguirre, Leopoldo Pan, Lang Hegde, Muralidhar L. Bácsi Attila (1967-) (immunológus) Hajas György (1970-) (biológus) Radák Zsolt Ba, Xueqing Mitra, Sankar Papaconstantinou, John Boldogh István
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11.

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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DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:

12.

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
Internet cím:Szerző által megadott URL
DOI
Intézményi repozitóriumban (DEA) tárolt változat
Borító:
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