British journal of anaesthesia : BJA, 2011-05, Vol.106 (5), p.650-658
2011
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- Autor(en) / Beteiligte
- Titel
- Effects of propofol on the expression of matric metalloproteinases in rat cardiac fibroblasts after hypoxia and reoxygenation
- Ist Teil von
- British journal of anaesthesia : BJA, 2011-05, Vol.106 (5), p.650-658
- Ort / Verlag
- Oxford: Elsevier Ltd
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- Propofol is known to protect the myocardium against ischaemia/reperfusion (I/R) injury through its antioxidant and anti-inflammatory properties. Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) are involved in cell migration and invasion, and mediate tissue remodelling during I/R injury. They are regulated by various mechanisms including oxidative stress and AKT and ERK pathways. We investigated whether propofol affected the expression of MMPs and subsequent cell migration and invasion and the signalling pathways involved in primary rat cardiac fibroblasts undergoing hypoxia and reoxygenation. The phosphorylation of ERK and AKT signalling pathways was examined by western blot analysis in rat primary cardiac fibroblasts after hypoxia and reoxygenation. mRNA expression of MMP and TIMPS was analysed by real-time PCR, and proteolytic activities of MMP-2 and -9 were assessed. The effects of propofol on migration, invasion, wound healing, and cell proliferation activity were evaluated after reoxygenation. Propofol induced AKT and ERK1/2 activation. Subsequent activation of MMPs resulted in increased cell migration, invasion, and wound-healing activity under hypoxia–reoxygenation, which was decreased by LY294002 (AKT inhibitor) and U0126 (ERK inhibitor) in rat cardiac fibroblasts. However, propofol had no effect on proliferation or viability of cardiac fibroblasts after hypoxia–reoxygenation. Propofol affected the expression of MMPs and TIMPs and subsequently induced cell migration and invasive ability, through activation of the ERK and AKT signalling pathway in hypoxia-reoxygenated rat cardiac fibroblasts.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0007-0912eISSN: 1471-6771DOI: 10.1093/bja/aer006Titel-ID: cdi_proquest_miscellaneous_862603364
- Format
- –
- Schlagworte
- Anesthesia, Anesthesia. Intensive care medicine. Transfusions. Cell therapy and gene therapy, Anesthetics, Intravenous - pharmacology, Animals, Biological and medical sciences, Cardiotonic Agents - pharmacology, Cell Hypoxia - physiology, Cell Movement - drug effects, Cell Proliferation - drug effects, Cell Survival - drug effects, Cells, Cultured, Extracellular Signal-Regulated MAP Kinases - drug effects, Extracellular Signal-Regulated MAP Kinases - metabolism, Fibroblasts - drug effects, Fibroblasts - enzymology, Gene Expression Regulation, Enzymologic - drug effects, ischaemia/reperfusion, matrix metalloproteinases, Matrix Metalloproteinases - biosynthesis, Matrix Metalloproteinases - drug effects, Matrix Metalloproteinases - genetics, Medical sciences, Myocardial Reperfusion Injury - enzymology, Myocardial Reperfusion Injury - pathology, propofol, Propofol - pharmacology, Proto-Oncogene Proteins c-akt - drug effects, Proto-Oncogene Proteins c-akt - metabolism, Rats, Rats, Sprague-Dawley, RNA, Messenger - genetics, Signal Transduction - drug effects, Tissue Inhibitor of Metalloproteinases - biosynthesis, Tissue Inhibitor of Metalloproteinases - drug effects, Tissue Inhibitor of Metalloproteinases - genetics