Mechanisms mediating the antiproliferative effects of nitric oxide in cultured human airway smooth muscle cells.
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.
Hamad
A M
AM
Department of Respiratory Medicine, Al-Mansourah University Hospital, Egypt.
Knox
A J
AJ
D015124:8-Bromo Cyclic Adenosine Monophosphate / Q000494:pharmacology; D001249:Asthma / Q000503:physiopathology; D001980:Bronchi / Q000166:cytology* / Q000187:drug effects; D002453:Cell Cycle / Q000502:physiology*; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free; D003839:Deoxyadenosines / Q000494:pharmacology; D003849:Deoxyguanosine / Q000494:pharmacology; D006454:Hemoglobins / Q000494:pharmacology; D006801:Humans; D008751:Methylene Blue / Q000494:pharmacology; D009130:Muscle, Smooth / Q000166:cytology* / Q000187:drug effects; D009569:Nitric Oxide / Q000378:metabolism*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology; D011688:Purinones / Q000494:pharmacology; D026423:S-Nitroso-N-Acetylpenicillamine / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism
D016895:Culture Media, Serum-Free; D003839:Deoxyadenosines; D006454:Hemoglobins; D020030:Nitric Oxide Donors; D010726:Phosphodiesterase Inhibitors; D011688:Purinones; D015124:8-Bromo Cyclic Adenosine Monophosphate; D009569:Nitric Oxide; D026423:S-Nitroso-N-Acetylpenicillamine; D003849:Deoxyguanosine; C011145:zaprinast; D008751:Methylene Blue; D013936:Thymidine