Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Resch, U; Schichl, YM; Sattler, S; de, Martin, R.
XIAP regulates intracellular ROS by enhancing antioxidant gene expression.
Biochem Biophys Res Commun. 2008; 375(1): 156-61.
Doi: 10.1016/j.bbrc.2008.07.142
Web of Science
PubMed
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- Co-Autor*innen der Med Uni Graz
- Sattler Susanne
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals - administration & dosage
- Antioxidants - metabolism
- Apoptosis - genetics
- Caspase 3 - metabolism
- Cells, Cultured - administration & dosage
- Gene Expression - drug effects
- Gene Expression Regulation - administration & dosage
- Hydrogen Peroxide - pharmacology
- MAP Kinase Kinase 4 - metabolism
- Mice - administration & dosage
- Mice, Mutant Strains - administration & dosage
- Oxidoreductases - genetics
- Poly(ADP-ribose) Polymerases - metabolism
- Reactive Oxygen Species - metabolism
- X-Linked Inhibitor of Apoptosis Protein - genetics, physiology
- Find related publications in this database (Keywords)
- XIAP
- ROS
- JNK
- apoptosis