| Title | The effect of cyclosporin A on the secretion of matrix metalloproteases by vascular smooth muscle cells is mediated by reactive oxygen species | |
| Author | E. Papakonstantinou1, U.T. Ruegg2, A. Aletras3, C. Pesintzaki1, P. Lhote2 and G. Karakiulakis1
1Laboratory of Pharmacology, School of Medicine, Aristotle University, Thessaloniki, Greece; 2Laboratory of Pharmacology, School of Pharmacy, University of Lausanne, Switzerland; 3Laboratory of Biochemistry, Department of Chemistry, University of Patras, Patra, Greece |
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| Citation | Papakonstantinou, E., Ruegg, U.T.,Aletras, A., Pesintzaki,C., Lhote, P., et al.: The effect of cyclosporin A on the secretion of matrix metalloproteases by vascular smooth muscle cells is mediated by reactive oxygen species, Epitheorese Klin. Farmakol. Farmakokinet. 18(1): 152-155 (2004) | |
| Publication Date | Accepted for publication: 2004 | |
| Full Text Language | English | |
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| Keywords | Cyclosporin A, CsA, Metalloproteases, Reactive Oxygen Species, ROS, Rat Aortic Smooth Muscle Cells, RASMC | |
| Other Terms | review article | |
| Summary | The clinical use of cyclosporin A (CsA) is limited due to its sever side effects such as nephrotoxicity and hypertension. It has been suggested that reactive oxygen species (ROS) may mediate the described side effects of CsA. In the present study, we investigated the effect of CsA on the secretion of gelatinases by rat aortic smooth muscle cells (RASMC) using gelatin zymography and ELISA. We found that CsA stimulated significantly the secretion of latent MMP-2, in a dose dependent manner, and this effect was most prominent after 46 h of incubation. H2O2 also induced by 2.3 fold the secretion of latent MMP-2 activity both at 16 and 46 h of incubation. The effect of CsA on the secretion of pro MMP-2 was inhibited in the presence of the antioxidant N-acetyl-L-cystein (NAC), indicating that CsA-induced secretion of pro MMP-2 is mediated by ROS. Treatment of the samples with 4-aminophenylmercuric acetate (APMA) prior to geatin zymography revealed that CsA downregulates TIMPs since more than 95% of the secreted latent pro MMP-2 exists in its free form. These data suggest that CsA regulates extracellular matrix turnover in RASMC which may be associated with its side effects in the cardiovascular system. | |
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Online ISSN 1011-6575
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