| Autor: |
Pahl, Paula M.B., Yan, Xiang-Dong, Hodges, Yvonne K., Rosenthal, Eli A., Horwitz, Marcus A., Horwitz, Lawrence D. |
| Zdroj: |
Journal of Biological Chemistry; June 2000, Vol. 275 Issue: 23 p17821-17826, 6p |
| Abstrakt: |
Proliferation of vascular smooth muscle cells (VSMC) is characteristic of restenosis following balloon angioplasty. We show here that a low concentration of a novel iron chelator, desferri-exochelin 772SM, reversibly arrests the growth of human VSMCin vitro, specifically in G0/G1and S phases. The lipophilic desferri-exochelin is effective more rapidly and at a 10-fold lower concentration than the nonlipophilic iron chelator deferoxamine. Treatment of growth-synchronized VSMC with the desferri-exochelin results in down-regulation of cyclin E/ Cdk2 and cyclin A/Cdk2 activity but does not affect the cyclin D/Cdk4/retinoblastoma phosphorylation pathway. Both DNA replication and RNA transcription are inhibited in exochelin-treated cells, but protein synthesis is not. The ability of desferri-exochelin 772SM to reversibly block the growth of VSMC in vitrowith no apparent cytotoxicity suggests that the exochelin may be useful as a therapeutic agent to limit restenosis in injured vessels. |
| Databáze: |
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