Role of reactive oxygen species in IL-1 beta-stimulated sustained ERK activation and MMP-9 induction
| Autor: | Milind V. Gurjar, Jason DeLeon, Ram V. Sharma, Ramesh C. Bhalla |
|---|---|
| Rok vydání: | 2001 |
| Předmět: |
MAPK/ERK pathway
Male medicine.medical_specialty Physiology MAP Kinase Signaling System Biology Matrix metalloproteinase Gene Expression Regulation Enzymologic Muscle Smooth Vascular Superoxide dismutase chemistry.chemical_compound Physiology (medical) Internal medicine medicine Extracellular Animals Enzyme Inhibitors Rats Wistar Cells Cultured chemistry.chemical_classification Flavonoids Reactive oxygen species Superoxide Superoxide Dismutase Genetic transfer Gene Transfer Techniques Free Radical Scavengers Cell biology Acetylcysteine Rats Endocrinology chemistry Matrix Metalloproteinase 9 biology.protein Signal transduction Mitogen-Activated Protein Kinases Cardiology and Cardiovascular Medicine Extracellular Space Reactive Oxygen Species Interleukin-1 |
| Zdroj: | American journal of physiology. Heart and circulatory physiology. 281(6) |
| ISSN: | 0363-6135 |
| Popis: | We have recently demonstrated that interleukin-1 beta (IL-1 beta) stimulates matrix metalloproteinase-9 (MMP-9) induction. In this study we have investigated the roles of superoxide and extracellular signal-regulated kinase (ERK) activation in MMP-9 induction following exposure to IL-1 beta. IL-1 beta stimulated biphasic ERK activation in vascular smooth muscle (VSM) cells, a transient activation that reached a maximum at 15 min and declined to baseline levels within 1 h, and a second phase of sustained ERK activation lasting up to 8 h. To determine the role of ERK in IL-1 beta-stimulated MMP-9 induction, we treated cells with the specific ERK pathway inhibitor PD-98059 at different time intervals after IL-1 beta stimulation. Addition of PD-98059 up to 4 h after IL-1 beta stimulation significantly inhibited MMP-9 induction, suggesting a role for sustained ERK activation in MMP-9 induction. IL-1 beta treatment stimulated superoxide production in VSM cells that was inhibited by pretreatment of cells with the superoxide scavenger N-acetyl-L-cysteine (NAC) and also by overexpression of the human manganese superoxide dismutase (MnSOD) gene. Treatment of VSM cells with NAC selectively inhibited the sustained phase of ERK activation without influencing the transient phase, suggesting a role for reactive oxygen species in sustained ERK activation. In addition, both NAC treatment and MnSOD overexpression significantly inhibited IL-1 beta-stimulated MMP-9 induction (P0.05). The results demonstrate that IL-1 beta-dependent MMP-9 induction is mediated by superoxide-stimulated ERK activation. |
| Databáze: | OpenAIRE |
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