| Title | SECIS binding protein 2 promotes cell survival by protecting against oxidative stress. | | Author(s) | Papp LV, Lu J, Bolderson E, Boucher D, Singh R, Holmgren A, Khanna KK | | Institution | The Queensland Institute of Medical Research, Cancer and Cell Biology Division, 300 Herston Road, Herston, Brisbane, Queensland, Australia, 4006, +61 7 38453738, +61 33620105; lauraP@qimr.edu.au. | | Source | Antioxid Redox Signal 2009 Oct 5. | | Abstract | Reactive oxygen species (ROS) are a primary cause of cellular damage that leads to cell death. In cells, protection from ROS-induced damage and maintenance of the redox balance is mediated to a large extent by selenoproteins, a distinct family of proteins that contain selenium in form of selenocysteine (Sec) within their active site. Incorporation of Sec requires the Sec insertion sequence element (SECIS) in the 3'-untranslated region of selenoproteins mRNAs and the SECIS binding protein 2 (SBP2). Previous studies have shown that SBP2 is required for the Sec incorporation mechanism; however, additional roles of SBP2 in the cell have remained undefined. We herein show that depletion of SBP2 using antisense oligonucleotides (ASOs) causes oxidative stress and induction of caspase- and cytochrome c-dependent apoptosis. Cells depleted of SBP2 have increased levels of ROS, which lead to cellular stress manifested as 8-oxo-7,8-dihydroguanine (8-oxo-dG) DNA lesions, stress granules and lipid peroxidation. Small molecule antioxidants N-acetylcysteine, glutathione, and alpha-tocopherol only marginally reduced ROS and were unable to fully rescue cells from apoptosis, indicating that apoptosis might be directly mediated by selenoproteins. Our results demonstrate that SBP2 is required for protection against ROS-induced cellular damage and cell survival. | | Language | ENG | | Pub Type(s) | JOURNAL ARTICLE
| | PubMed ID | 19803747 |
|
