title: Different anti-oxidant effects of thioredoxin 1 and thioredoxin 2 in retinal epithelial cells.
abstract: Age-related macular degeneration (AMD) affects the retina and is the most common cause of blindness in elderly persons in developed countries. The retina is constantly subjected to oxidative stress; to avoid the effects of oxidative stress, retinal pigment epithelial (RPE) cells possess potent anti-oxidant systems. Disruption of these systems leads to dysfunction of RPE cells, which then accelerates the development of AMD. Here, we investigated the role of thioredoxins (TRXs), scavengers of intracellular reactive oxygen species, by assessing the effect of TRX overexpression on cell viability, morphology, NF-κB expression, and mitochondrial membrane potential, in RPE cells. TRX-overexpressing cell lines were generated by infection of an established human RPE cell line (ARPE) with adeno-associated virus vectors encoding either TRX1 or TRX2. We showed that overexpression of TRXs reduced cell death caused by 4-hydroxynonenal (4-HNE)-induced oxidative stress; TRX2 was more effective than TRX1 in promoting cell survival. 4-HNE caused perinuclear NF-κB accumulation, which was absent in TRX-overexpressing cells. Moreover, overexpression of TRXs prevented depolarization of mitochondrial membranes; again, TRX2 was more effective than TRX1 in maintaining the membrane potential. The difference in the protective effects of these TRXs against oxidative stress may be due to their expression profile. TRX2 was expressed in the mitochondria, while TRX1 was expressed in the cytoplasm. Thus, TRX2 may directly protect mitochondria by preventing depolarization. These results demonstrate that TRXs are potent antioxidant proteins in RPE cells and their direct effect on mitochondria may be a key to prevent oxidative stress.
authors.affiliation: Department of Chemistry and Bioengineering, Faculty of Engineering, Graduate School of Engineering, Iwate University, Iwate, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Sugano
authors.forename: Hitomi
authors.initials: H
authors.lastname: Isago
authors.forename: Namie
authors.initials: N
authors.lastname: Murayama
authors.forename: Makoto
authors.initials: M
authors.lastname: Tamai
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Tomita
mesh_terms: D000447:Aldehydes / Q000494:pharmacology; D000975:Antioxidants; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D006801:Humans; D008268:Macular Degeneration; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D017382:Reactive Oxygen Species / Q000378:metabolism; D012160:Retina / Q000166:cytology / Q000378:metabolism; D055213:Retinal Pigment Epithelium / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics / Q000378:metabolism
chemical_list: D000447:Aldehydes; D000975:Antioxidants; D016328:NF-kappa B; D017382:Reactive Oxygen Species; D013879:Thioredoxins; C027576:4-hydroxy-2-nonenal