NDLI: Polyamine synthesis inhibition induces S phase cell cycle arrest in vascular smooth muscle cells

Content Provider	Springer Nature Link
Author	Odenlund, M. Holmqvist, B. Baldetorp, B. Hellstrand, P. Nilsson, Bengt Olof
Copyright Year	2008
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.
Starting Page	273
Ending Page	282
Page Count	10
File Format	PDF
ISSN	09394451
Journal	Amino Acids
Volume Number	36
Issue Number	2
e-ISSN	14382199
Language	English
Publisher	Springer Vienna
Publisher Date	2008-03-27
Publisher Place	Vienna
Access Restriction	Subscribed
Subject Keyword	Arginase Cell cycle distribution DNA synthesis Ornitihine decarboxylase Polyamines Vascular smooth muscle cells Neurobiology Proteomics Life Sciences Biochemical Engineering Analytical Chemistry Biochemistry
Content Type	Text
Resource Type	Article
Subject	Organic Chemistry Biochemistry Clinical Biochemistry

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