scholarly journals Lipopolysaccharide-induced murine embryonic resorption involves nitric oxide-mediated inhibition of the NAD+-dependent 15-hydroxyprostaglandin dehydrogenase

Reproduction ◽  
2012 ◽  
Vol 144 (4) ◽  
pp. 447-454 ◽  
Author(s):  
Julieta Aisemberg ◽  
María V Bariani ◽  
Claudia A Vercelli ◽  
Manuel L Wolfson ◽  
Ana M Franchi
Keyword(s):  
Nitric Oxide ◽  
Protein Expression ◽  
Pregnancy Loss ◽  
Nitric Oxide Donor ◽  
Biological Processes ◽  
Inflammatory Condition ◽  
Nitric Oxide Synthesis ◽  
Uterine Tissue ◽  
Embryonic Resorption ◽  
Oxide Synthase

The initial inactivation of prostaglandins (PGs) is mediated by 15-hydroxyprostaglandin dehydrogenase (15-PGDH). PGs are potent mediators of several biological processes, including inflammation and reproduction. In uterus, PGs play a key role in infection-induced pregnancy loss, in which concentration of this mediator increased. This process is accompanied with the induction of nitric oxide synthase expression and a marked increase in uterine levels of nitric oxide. There is no information concerning nitric oxide contribution to potential changes in PG catabolism, but experimental evidence suggests that nitric oxide modulates PG pathways. The specific objectives of the study were to evaluate the protein expression of HPGD (15-PGDH) and to characterize the nitric oxide-dependent regulation of this enzyme in a model of lipopolysaccharide (LPS)-induced embryonic resorption. Results show that LPS decreased HPGD protein expression and augmented PGE synthase activity; therefore, PGE2 levels increased in uterus in this inflammatory condition. Just as LPS, the treatment with a nitric oxide donor diminished HPGD protein expression in uterine tissue. In contrast, the inhibition of nitric oxide synthesis both in control and in LPS-treated mice increased 15-PGDH levels. Also, we have found that this enzyme and PGE2 levels are not modulated by peroxynitrite, an oxidant agent derived from nitric oxide. This study suggests that LPS and nitric oxide promote a decrease in the ability of the uterus for PG catabolism during bacterially triggered pregnancy loss in mice.

Inhibition of tetrahydrobiopterin biosynthesis impairs endothelium-dependent relaxations in canine basilar artery

1997 ◽  
Vol 273 (2) ◽  
pp. H718-H724 ◽  
Author(s):  
H. Kinoshita ◽  
S. Milstien ◽  
C. Wambi ◽  
Z. S. Katusic
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Nitric Oxide Synthase ◽  
Endothelial Function ◽  
Isometric Force ◽  
Cerebral Arteries ◽  
Calcium Ionophore ◽  
Nitric Oxide Donor ◽  
Ionophore A23187 ◽  
Oxide Synthase

Tetrahydrobiopterin is an essential cofactor in biosynthesis of nitric oxide. The present study was designed to determine the effect of decreased intracellular tetrahydrobiopterin levels on endothelial function of isolated cerebral arteries. Blood vessels were incubated for 6 h in minimum essential medium (MEM) in the presence or absence of a GTP cyclohydrolase I inhibitor, 2,4-diamino-6-hydroxypyrimidine (DAHP, 10(-2) M). Rings with and without endothelium were suspended for isometric force recording in the presence of a cyclooxygenase inhibitor, indomethacin (10(-5) M). In arteries with endothelium, DAHP significantly reduced intracellular levels of tetrahydrobiopterin. DAHP in combination with a precursor of the salvage pathway of tetrahydrobiopterin biosynthesis, sepiapterin (10(-4) M), not only restored but increased levels of tetrahydrobiopterin above control values. In DAHP-treated arteries, endothelium-dependent relaxations to bradykinin (10(-10)-10(-6) M) or calcium ionophore A23187 (10(-9)-10(-6) M) were significantly reduced, whereas endothelium-independent relaxations to a nitric oxide donor, 3-morpholinosydnonimine (10(-9)-10(-4) M), were not affected. When DAHP-treated arteries with endothelium were incubated with sepiapterin (10(-4) M) or superoxide dismutase (150 U/ml), relaxations to bradykinin and A23187 were restored to control levels. In contrast, superoxide dismutase did not affect endothelium-dependent relaxations in arteries incubated in MEM. A nitric oxide synthase inhibitor, NG-nitro-L-arginine methyl ester (10(-4) M), abolished relaxations to bradykinin or A23187 in control arteries and in DAHP-treated arteries. These studies demonstrate that in cerebral arteries, decreased intracellular levels of tetrahydrobiopterin can reduce endothelium-dependent relaxations. Production of superoxide anions during activation of dysfunctional endothelial nitric oxide synthase appears to be responsible for the impairment of endothelial function.

scholarly journals TRPV3 regulates nitric oxide synthase-independent nitric oxide synthesis in the skin

2011 ◽  
Vol 2 (1) ◽  
Author(s):  
Takashi Miyamoto ◽  
Matt J. Petrus ◽  
Adrienne E. Dubin ◽  
Ardem Patapoutian
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitric Oxide Synthesis ◽  
Oxide Synthase

Nitric oxide synthase and arginase expression changes in the rat perirhinal and entorhinal cortices following unilateral vestibular damage: A link to deficits in object recognition?

2004 ◽  
Vol 14 (6) ◽  
pp. 411-417 ◽  
Author(s):  
Ping Liu ◽  
Catherine M. Gliddon ◽  
Libby Lindsay ◽  
Cynthia L. Darlington ◽  
Paul F. Smith
Keyword(s):  
Nitric Oxide ◽  
Object Recognition ◽  
Nitric Oxide Synthase ◽  
Protein Expression ◽  
Medial Temporal Lobe ◽  
Contralateral Side ◽  
Arginase Ii ◽  
Neurochemical Changes ◽  
Oxide Synthase ◽  
Vestibular Damage

Previous studies have shown that peripheral vestibular damage causes long-term neurochemical changes in the hippocampus which may be related to spatial memory deficits. Since recent studies have also demonstrated deficits in non-spatial object recognition memory following vestibular lesions, the aim of the present study was to extend these investigations into the perirhinal cortex (PRC), which is known to be important for object recognition, and the related entorhinal cortex (EC). We examined the effects of unilateral vestibular deafferentation (UVD) on the expression of four enzymes associated with neuronal plasticity, neuronal nitric oxide synthase (nNOS), endothelial nitric oxide synthase (eNOS), arginase I and arginase II (AI and II), in the rat EC and PRC using Western blotting. Tissue was collected at 10 hs, 50 hs and 2 weeks post-UVD. In the EC and PRC, nNOS protein expression decreased on the contralateral side at 2 weeks post-UVD but not before. At the same time, eNOS protein expression increased in both regions on the contralateral side. In the EC, AII protein expression increased on the ipsilateral side at 2 weeks post-UVD. In the PRC, AI increased and decreased on the contralateral and ipsilateral sides (respectively) at 2 weeks post-UVD. AII showed a bilateral increase in the PRC at 2 weeks post-UVD. These results demonstrate changes in NOS and arginase protein expression in the PRC and EC following UVD, which are unlikely to be due to the initial severity of the vestibular syndrome because they develop well after vestibular compensation has taken place. Neurochemical changes in these regions of the medial temporal lobe may be implicated in the development of object recognition deficits that contribute to cognitive dysfunction following peripheral vestibular damage.

Maturation alters cerebral NOS kinetics in the spontaneously hypertensive rat

1997 ◽  
Vol 273 (4) ◽  
pp. R1367-R1373 ◽  
Author(s):  
William J. Pearce ◽  
Beatriz Tone ◽  
Stephen Ashwal
Keyword(s):  
Nitric Oxide ◽  
Spontaneously Hypertensive Rat ◽  
Neuronal Nitric Oxide Synthase ◽  
Nitric Oxide Synthesis ◽  
Hypertensive Rats ◽  
General Hypothesis ◽  
Spontaneously Hypertensive ◽  
Age Related ◽  
Oxide Synthase ◽  
Menten Constant

Using14C-labeled arginine to14C-labeled citrulline conversion assays in brain homogenates from 14- to 18-day-old and adult spontaneously hypertensive rats, we tested the hypotheses that maturation increases neuronal nitric oxide synthase (nNOS) activity and that this increase involves changes in cofactor availability and/or nNOS kinetics. nNOS activity (in pmol ⋅ mg−1 ⋅ min−1) was 46% higher in adults (19 ± 2) than in pups (13 ± 1). The addition of 264 μM calmodulin (CaM), 3 μM FAD, 3 μM flavin adenine mononucleotide (FMN), and 10 μM tetrahydrobiopterin (BH4) increased NOS activity by 3, 46, 45, and 88% in pups and by 19, 40, 36, and 102% in adults, respectively. All cofactor effects were significant except for CaM in the pup homogenates. Cofactor effects were not significantly different between pup and adult homogenates, except for BH4, which increased absolute NOS activity more in adults than in pups. Values of maximal enzyme velocity ( V max) for nNOS in the absence of added cofactors were greater in adults than in pups (104 ± 5 vs. 53 ± 3, P < 0.05). Addition of 3 μM FAD or 3 μM FMN increased pup V max values to 68 ± 2 and 99 ± 5, respectively, but had no effect in adults. BH4 did not affect V max in either group. Control values of the Michaelis-Menten constant ( K m) forl-arginine were greater ( P < 0.05) in pups (5.7 ± 0.4 μM) than in adults (4.3 ± 0.2 μM) and were significantly reduced by 10 μM BH4 to 3.8 ± 0.2 and 2.9 ± 0.1 μM, respectively. Neither FAD nor FMN affected K mvalues in either group. The results indicate that endogenous nNOS cofactor levels are not saturating in either pups or adults, changes in cofactor levels differentially affect NOS kinetics in pups and adults, and age-related differences in NOS activity result from fundamental differences in NOS kinetics. These findings support the general hypothesis that the increased vulnerability to ischemic stroke associated with maturation is due in part to corresponding increases in the capacity for nitric oxide synthesis.

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