Nitric oxide and cyclic GMP as pro- and anti-apoptotic agents.
BACKGROUND
Previously we showed that atrial natriuretic peptide (ANP) increases cGMP production in PC12 (sympathetic-neuron-like) cells, cGMP elevations increase survival of hippocampal neurons during glutamate toxicity and ANP-induced cGMP elevations prolongs survival of stressed PC12 cells, all suggesting cGMP mediates anti-apoptotic/pro-survival effects in neural cells.


OBJECTIVE
The objective was to use a new technology, capillary electrophoresis-laser-induced-fluorescence-detector (CE-LIF) to accurately measure nitric oxide (NO)-induced stimulation and ANP/cGMP-induced inhibition of apoptotic DNA fragmentation in PC12 and NG108-15 (cholinergic-neuron-like) cells.


METHODS
Apoptotic DNA fragmentation was quantified by CE-LIF.


RESULTS
Sodium nitroprusside (SNP, 0.1-1.0 mM, 24 hours), NO donor, increased apoptotic DNA fragmentation in NG108-15 cells, but not PC12 cells (both with serum). In serum-deprived PC12 cells, ANP at 1, 10 and 100 nM inhibited apoptotic DNA fragmentation by 75.8%, 84.7%, and 94.1%, respectively.


CONCLUSIONS
The data show that NO at higher levels induces apoptosis in NG108-15 cells, but not PC12 cells, indicating differences in susceptibility to NO-induced toxicity, and that ANP-induced cGMP elevation is a potent and effective inhibitor of apoptosis in PC12 cells. The data suggest that NO-induced cGMP elevations in certain neural cells (e.g. PC12 cells) provide a protective (anti-apoptotic) mechanism that counter-balances the pro-apoptotic actions of NO, thus helping to limit damage caused by NO.
Fiscus
Ronald R
RR
Department of Physiology, Faculty of Medicine, The Chinese University of Hong Kong, Shatin, NT, Hong Kong. ronfiscus@cuhk.edu.hk
Yuen
Jessie P S
JP
Chan
Siu Lan
SL
Kwong
Joyce H Y
JH
Chew
Siew Boon Cheng
SB
D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D009320:Atrial Natriuretic Factor / Q000097:blood / Q000494:pharmacology; D006152:Cyclic GMP / Q000378:metabolism* / Q000494:pharmacology*; D053938:DNA Fragmentation / Q000187:drug effects; D004587:Electrophoresis, Agar Gel; D019075:Electrophoresis, Capillary; D023421:Models, Animal; D009569:Nitric Oxide / Q000378:metabolism* / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D009599:Nitroprusside / Q000494:pharmacology; D016716:PC12 Cells / Q000187:drug effects / Q000378:metabolism; D051381:Rats
D020030:Nitric Oxide Donors; D009599:Nitroprusside; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D006152:Cyclic GMP