| First Author | Baek JY | Year | 2012 |
| Journal | J Biol Chem | Volume | 287 |
| Issue | 1 | Pages | 81-9 |
| PubMed ID | 22086924 | Mgi Jnum | J:179205 |
| Mgi Id | MGI:5301459 | Doi | 10.1074/jbc.M111.316711 |
| Citation | Baek JY, et al. (2012) Sulfiredoxin Protein Is Critical for Redox Balance and Survival of Cells Exposed to Low Steady-state Levels of H2O2. J Biol Chem 287(1):81-9 |
| abstractText | Sulfiredoxin (Srx) is an enzyme that catalyzes the reduction of cysteine sulfinic acid of hyperoxidized peroxiredoxins (Prxs). Having high affinity toward H(2)O(2), 2-Cys Prxs can efficiently reduce H(2)O(2) 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 H(2)O(2). Here we examine the novel role of Srx in cells exposed to low steady-state levels of H(2)O(2), which can be achieved by using glucose oxidase. Exposure of low steady-state levels of H(2)O(2) (10-20 mum) 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 H(2)O(2) 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 H(2)O(2), 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 H(2)O(2). These results indicate that Srx functions as a novel component to maintain the balance between H(2)O(2) production and elimination and then protects cells from apoptosis even in the presence of low steady-state levels of H(2)O(2). |
