Polyamine synthesis inhibition induces S phase cell cycle arrest in vascular smooth muscle cells |
| |
Authors: | M Odenlund B Holmqvist B Baldetorp P Hellstrand Bengt-Olof Nilsson |
| |
Institution: | (1) Department of Experimental Medical Science, Division of Vascular and Airway Research, Unit of Vascular Physiology, Lund University, BMC D12, 221 84 Lund, Sweden;(2) Department of Clinical Sciences, Unit of Oncology, Lund University Hospital, Lund University, 221 85 Lund, Sweden; |
| |
Abstract: | Polyamines are important for cell growth and proliferation and they are formed from arginine and ornithine via arginase and
ornithine decarboxylase (ODC). Arginine may alternatively be metabolised to NO via NO synthase. Here we study if vascular
smooth muscle cell proliferation can be reversed by polyamine synthesis inhibitors and investigate their mechanism of action.
Cell proliferation was assessed in cultured vascular smooth muscle A7r5 cells and in endothelium-denuded rat arterial rings
by measuring 3H]-thymidine incorporation and by cell counting. Cell cycle phase distribution was determined by flow cytometry and polyamines
by HPLC. Protein expression was determined by Western blotting. The ODC inhibitor DFMO (1–10 mM) reduced polyamine concentration
and attenuated proliferation in A7r5 cells and rat tail artery. DFMO accumulated cells in S phase of the cell cycle and reduced
cyclin A expression. DFMO had no effect on cell viability and apoptosis as assessed by fluorescence microscopy. Polyamine
concentration and cellular proliferation were not affected by the arginase inhibitor NOHA (100–200 μM) and the NO synthase
inhibitor l-NAME (100 μM). Lack of effect of NOHA was reflected by absence of arginase expression. Polyamine synthesis inhibition attenuates
vascular smooth muscle cell proliferation by reducing DNA synthesis and accumulation of cells in S phase, and may be a useful
approach to prevent vascular smooth muscle cell proliferation in cardiovascular diseases. |
| |
Keywords: | |
本文献已被 PubMed SpringerLink 等数据库收录! |
|