title: Sulfiredoxin protein is critical for redox balance and survival of cells exposed to low steady-state levels of H2O2.
abstract: Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of cysteine sulfinic acid of hyperoxidized peroxiredoxins (Prxs). Having high affinity toward H2O2, 2-Cys Prxs can efficiently reduce H2O2 at low concentration. We previously showed that Prx I is hyperoxidized at a rate of 0.072% per turnover even in the presence of low steady-state levels of H2O2. Here we examine the novel role of Srx in cells exposed to low steady-state levels of H2O2, which can be achieved by using glucose oxidase. Exposure of low steady-state levels of H2O2 (10-20 μm) to A549 or wild-type mouse embryonic fibroblast (MEF) cells does not lead to any significant change in oxidative injury because of the maintenance of balance between H2O2 production and elimination. In contrast, loss-of-function studies using Srx-depleted A549 and Srx-/- MEF cells demonstrate a dramatic increase in extra- and intracellular H2O2, sulfinic 2-Cys Prxs, and apoptosis. Concomitant with hyperoxidation of mitochondrial Prx III, Srx-depleted cells show an activation of mitochondria-mediated apoptotic pathways including mitochondria membrane potential collapse, cytochrome c release, and caspase activation. Furthermore, adenoviral re-expression of Srx in Srx-depleted A549 or Srx-/- MEF cells promotes the reactivation of sulfinic 2-Cys Prxs and results in cellular resistance to apoptosis, with enhanced removal of H2O2. These results indicate that Srx functions as a novel component to maintain the balance between H2O2 production and elimination and then protects cells from apoptosis even in the presence of low steady-state levels of H2O2.
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Baek
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Sun Hee
authors.initials: SH
authors.lastname: Han
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Su Haeng
authors.initials: SH
authors.lastname: Sung
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Hye Eun
authors.initials: HE
authors.lastname: Lee
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Yu-Mi
authors.initials: YM
authors.lastname: Kim
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: You Hyun
authors.initials: YH
authors.lastname: Noh
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Soo Han
authors.initials: SH
authors.lastname: Bae
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea.
authors.forename: Sue Goo
authors.initials: SG
authors.lastname: Rhee
authors.affiliation: Division of Life and Pharmaceutical Sciences and Center for Cell Signaling and Drug Discovery Research, Ewha Womans University, Seoul 120-750, Korea; College of Pharmacy, Ewha Womans University, Seoul, 120-750, Korea. Electronic address: changts@ewha.ac.kr.
authors.forename: Tong-Shin
authors.initials: TS
authors.lastname: Chang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D045304:Cytochromes c / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D055786:Gene Knockout Techniques; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism / Q000494:pharmacology*; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects; D051379:Mice; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D050862:Oxidoreductases Acting on Sulfur Group Donors / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D034741:RNA, Small Interfering; D045304:Cytochromes c; D006861:Hydrogen Peroxide; D050862:Oxidoreductases Acting on Sulfur Group Donors; C529381:sulfiredoxin protein, mouse; D053148:Caspase 3; D053453:Caspase 9
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