| First Author | Resch U | Year | 2008 |
| Journal | Biochem Biophys Res Commun | Volume | 375 |
| Issue | 1 | Pages | 156-61 |
| PubMed ID | 18692482 | Mgi Jnum | J:140321 |
| Mgi Id | MGI:3813375 | Doi | 10.1016/j.bbrc.2008.07.142 |
| Citation | Resch U, et al. (2008) XIAP regulates intracellular ROS by enhancing antioxidant gene expression. Biochem Biophys Res Commun 375(1):156-61 |
| abstractText | XIAP (X chromosome-linked inhibitor of apoptosis) is a member of the anti-apoptotic IAP gene family and an inhibitor of caspase-3. We show here that loss of XIAP renders cells highly sensitive to oxidative stress. Stimulation of XIAP(-/-) MEF with hydrogen peroxide, or other agents that generate reactive oxygen species (ROS) results in increased apoptosis assessed by caspase-3 activity and PARP cleavage. Furthermore, we observed increased levels of ROS and diminished expression of antioxidative genes, e.g., SOD1, -2, NQO1, HO-1, and Txn2 in XIAP(-/-) cells. In addition, stimulation of XIAP(-/-) MEF with hydrogen peroxide resulted in enhanced phosphorylation of JNK. Our findings reveal that XIAP, in addition to its well described caspase-inhibitory function, prevents prolonged JNK activation and is critically involved in modulating ROS levels through regulation of antioxidative genes, thereby inhibiting ROS-induced apoptosis. |
