As. Vidwans et al., Differential modulation of prostaglandin H synthase-2 by nitric oxide-related species in intact cells, BIOCHEM, 40(38), 2001, pp. 11533-11542
Nitrogen monoxide (NO) has been reported to both activate and inhibit prost
aglandin (PG) biosynthesis. This apparent paradox might be explained by the
production/action of distinct NO-related species formed as a result of the
prevailing redox states of different cellular systems. As such, the effect
of NO donors with different redox characteristics on the modulation of pro
staglandin H synthase-2 (PGHS-2) in primary mouse cortical astrocytes and C
OS-7 cells engineered to overexpress PGHS-2 was assessed. In general, compo
unds that released NO. or NO- enhanced, while a peroxynitrite (OONO-) gener
ator inhibited, PGHS-2-dependent prostaglandin production. While the possib
ility of altered gene transcription was eliminated in the COS-7 system as P
GHS-2 was maximally expressed, in primary astrocytes where PGHS-2 expressio
n was induced by lipopolysaccharide (LPS), effects on protein expression we
re detected. Compounds that released NO. synergistically enhanced LPS-media
ted PGHS-2 protein synthesis. None of these effects were mediated by cGMP.
All donors lost their ability to modulate PGHS-2 expression and function wh
en decayed. These results indicate that the ultimate effect of NO on PGHS-2
enzyme activity and expression is dictated by the prevalent NO-related spe
cies formed, suggesting that important interactions which may exist between
NO and prostanoid pathways in vivo will be highly dependent on the inheren
t redox environment.