title: Increased resistance to oxidative DNA damage of trabecular meshwork cells by E. coli FPG gene transfection.
abstract: Oxidative damage plays a pathogenic role in various chronic degenerative diseases. Oxidative damage targeting trabecular meshwork (TM) cells as a consequence of mitochondrial damage is a pathogenic mechanism for glaucoma, the most common cause of irreversible blindness worldwide. Consequences of oxidative damage are attenuated by endocellular activities involved in scavenging reactive oxidative species and DNA repair. Selected bacterial genes are highly efficient at protecting cells from oxidative DNA damage. This situation occurs for Escherichia coli formamidopyrimidine DNA glycosylase (FPG), a major DNA glycosylase that repairs oxidatively damaged DNA. Accordingly, this study was aimed at transfecting human TM cells (HTMC) with Fpg in order to increase their resistance to oxidative damage. This study demonstrates that it is feasible to increase resistance of HTMC to endogenous oxidative damage by gene transfection. These findings bear relevance for primary and secondary prevention of degenerative glaucomas and other degenerative diseases where oxidative damage plays a pathogenic role.
authors.affiliation: Molecular Mutagenesis & DNA Repair Unit, Istituto Nazionale Ricerca Cancro, Genoa, Italy.
authors.forename: M
authors.initials: M
authors.lastname: Foresta
authors.forename: G
authors.initials: G
authors.lastname: Frosina
authors.forename: S C
authors.initials: SC
authors.lastname: Sacca
authors.forename: C
authors.initials: C
authors.lastname: Cartiglia
authors.forename: M
authors.initials: M
authors.lastname: Longobardi
authors.forename: A
authors.initials: A
authors.lastname: Izzotti
mesh_terms: D000080242:8-Hydroxy-2'-Deoxyguanosine; D045744:Cell Line, Tumor; D004249:DNA Damage; D043382:DNA-Formamidopyrimidine Glycosylase / Q000235:genetics*; D003849:Deoxyguanosine / Q000031:analogs & derivatives / Q000032:analysis; D042783:Endothelial Cells / Q000378:metabolism; D004926:Escherichia coli / Q000235:genetics* / Q000378:metabolism*; D029968:Escherichia coli Proteins / Q000235:genetics*; D015870:Gene Expression; D015316:Genetic Therapy; D005901:Glaucoma / Q000235:genetics / Q000517:prevention & control / Q000628:therapy; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000235:genetics; D014129:Trabecular Meshwork / Q000166:cytology / Q000378:metabolism*; D014162:Transfection
chemical_list: D029968:Escherichia coli Proteins; D017382:Reactive Oxygen Species; D011993:Recombinant Fusion Proteins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D043382:DNA-Formamidopyrimidine Glycosylase; C468610:DNA-formamidopyrimidine glycosylase, E coli; D003849:Deoxyguanosine