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Mechanisms mediating the antiproliferative effects of nitric oxide in cultured human airway smooth muscle cells
Author(s) -
Hamad Ahmed M,
Knox Alan J
Publication year - 2001
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(01)02883-6
Subject(s) - zaprinast , nitric oxide , phosphodiesterase 3 , ribonucleotide reductase , chemistry , phosphodiesterase , cyclic guanosine monophosphate , penicillamine , scavenger , cell growth , cell cycle , phosphodiesterase inhibitor , microbiology and biotechnology , cell , biochemistry , biology , enzyme , protein subunit , radical , organic chemistry , gene
We have characterised the mechanisms involved in the antiproliferative effect of NO in human airway smooth muscle cells (HASMC). S ‐Nitroso‐ N ‐acetyl penicillamine, a nitric oxide donor, inhibited proliferation in both G 1 and S phases of the cell cycle. Additionally, experiments with 8‐bromo‐cGMP, haemoglobin, a NO scavenger and zaprinast, a cGMP‐specific phosphodiesterase inhibitor, showed that both effects were NO‐mediated. The G 1 phase inhibition was cGMP‐dependent whereas the S phase inhibition was due to a cGMP‐independent inhibition of ribonucleotide reductase. These results demonstrate that NO inhibits HASMC proliferation by cGMP‐dependent and ‐independent mechanisms acting at distinct points in the cell cycle.