Antioxidant potential of CORM-A1 and resveratrol during TNF-α/cycloheximide-induced oxidative stress and apoptosis in murine intestinal epithelial MODE-K cells
| Autor: | Roberto Motterlini, Georges Leclercq, Peter Vandenabeele, Vera Goossens, Dinesh Babu, Romain Lefebvre, Quinten Remijsen |
|---|---|
| Rok vydání: | 2015 |
| Předmět: |
Mitochondrial ROS
Anti-Inflammatory Agents Carbonates Apoptosis Oxidative phosphorylation Mitochondrion Resveratrol Toxicology medicine.disease_cause Antioxidants Cell Line chemistry.chemical_compound Mice Oxygen Consumption Superoxides Stilbenes medicine Animals Cycloheximide Intestinal Mucosa Boranes Pharmacology chemistry.chemical_classification Membrane Potential Mitochondrial Reactive oxygen species NADPH oxidase biology Tumor Necrosis Factor-alpha NADPH Oxidases Epithelial Cells Cell biology Mitochondria Oxidative Stress chemistry Biochemistry Cytoprotection biology.protein Oxidative stress Intracellular |
| Zdroj: | Toxicology and applied pharmacology. 288(2) |
| ISSN: | 1096-0333 |
| Popis: | Targeting excessive production of reactive oxygen species (ROS) could be an effective therapeutic strategy to prevent oxidative stress-associated gastrointestinal inflammation. NADPH oxidase (NOX) and mitochondrial complexes (I and II) are the major sources of ROS production contributing to TNF-α/cycloheximide (CHX)-induced apoptosis in the mouse intestinal epithelial cell line, MODE-K. In the current study, the influence of a polyphenolic compound (resveratrol) and a water-soluble carbon monoxide (CO)-releasing molecule (CORM-A1) on the different sources of TNF-α/CHX-induced ROS production in MODE-K cells was assessed. This was compared with H2O2-, rotenone- or antimycin-A-induced ROS-generating systems. Intracellular total ROS, mitochondrial-derived ROS and mitochondrial superoxide anion (O2 −) production levels were assessed. Additionally, the influence on TNF-α/CHX-induced changes in mitochondrial membrane potential (Ψm) and mitochondrial function was studied. In basal conditions, CORM-A1 did not affect intracellular total or mitochondrial ROS levels, while resveratrol increased intracellular total ROS but reduced mitochondrial ROS production. TNF-α/CHX- and H2O2-mediated increase in intracellular total ROS production was reduced by both resveratrol and CORM-A1, whereas only resveratrol attenuated the increase in mitochondrial ROS triggered by TNF-α/CHX. CORM-A1 decreased antimycin-A-induced mitochondrial O2 − production without any influence on TNF-α/CHX- and rotenone-induced mitochondrial O2 − levels, while resveratrol abolished all three effects. Finally, resveratrol greatly reduced and abolished TNF-α/CHX-induced mitochondrial depolarization and mitochondrial dysfunction, while CORM-A1 only mildly affected these parameters. These data indicate that the cytoprotective effect of resveratrol is predominantly due to mitigation of mitochondrial ROS, while CORM-A1 acts solely on NOX-derived ROS to protect MODE-K cells from TNF-α/CHX-induced cell death. This might explain the more pronounced cytoprotective effect of resveratrol. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|
Full Text from ScienceDirect