Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Koga, Toshikatsu; Koshiyama, Yasuo; Gotoh, Tomomi; Yonemura, Naoko; Hirata, Akira; Tanihara, Hidenobu; Negi, Akira; Mori, Masataka

doi:10.1006/exer.2002.2062

Cited by 35 publications

(21 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this report, we used an intravitreal injection of the endotoxin since this maneuver avoids systemic inflammations and allows the use of the contralateral eye (which did not show clinical or histological changes in comparison with non-injected eyes [data not shown]) as control, minimizing the number of animals, and decreasing their mortality. As described in other species, 8,43 the intravitreal injection of LPS in the golden hamster induced several signs of uveitis such as disruption of the BOB, dilatation of conjunctival vessels, iridial hyperemia, and flare in the anterior chamber. In addition to these anterior segment (anterior chamber, iris, and ciliary body) alterations, the examination of the posterior segment showed retinal vasculitis, hemorrhagic exudates, focal destruction of photoreceptors, and retinal infiltration.…”

Section: Discussionsupporting

confidence: 54%

Therapeutic Effect of Melatonin in Experimental Uveitis

Sande

Fernandez

Marcos

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

Uveitis is a common ophthalmic disorder that can be induced in hamsters by a single intravitreal injection of bacterial lipopolysaccharide (LPS). To examine the therapeutic effects of melatonin on uveitis, a pellet of melatonin was implanted subcutaneously 2 hours before the intravitreal injection of either vehicle or LPS. Both 24 hours and 8 days after the injection, inflammatory responses were evaluated in terms of i) the integrity of the blood-ocular barrier, ii) clinical signs, iii) histopathological studies, and iv) retinal function. Melatonin reduced the leakage of proteins and cells in the anterior segment of LPS-injected eyes, decreased clinical signs such as dilation of the iris and conjunctival vessels, and flare in the anterior chamber, and protected the ultrastructure of the blood-ocular barrier. A remarkable disorganization of rod outer segment membranous disks was observed in animals injected with LPS, whereas no morphological changes in photoreceptor outer segments were observed in animals treated with melatonin. Furthermore, melatonin prevented a decrease in LPS-induced electroretinographic activity. In addition, melatonin significantly abrogated the LPS-induced increase in retinal nitric-oxide synthase activity, tumor necrosis factor-␣, and nuclear factor B p50 and p65 subunit levels. These results indicate that melatonin prevents the clinical, biochemical, histological, ultrastructural, and functional consequences of experimental uveitis, likely through a nuclear factor B-dependent mechanism, and support the use of melatonin as a new therapeutic strategy for the treatment of uveitis. (Am J Pathol

show abstract

Section: Discussionsupporting

confidence: 54%

Therapeutic Effect of Melatonin in Experimental Uveitis

Sande

Fernandez

Marcos

et al. 2008

The American Journal of Pathology

View full text Add to dashboard Cite

show abstract

“…Argininosuccinate synthetase (ASS, EC 6.3.4.5) needs citrulline, as well as aspartate, for the rate-limiting step in arginine biosynthesis [25], so decreased ASS activity would result in an increase in citrulline concentration. This enzyme is co-induced with NOS II during an immune response [25,30,31] because citrulline recycling to arginine is important to maintain up to 80% of NO biosynthesis, at least in endothelial cells under bradykinin stimulation [28]. Also, the fact that citrulline and NOS co-localize in the CNS [26], but NOS and ASS do not in most neurons [32] suggests that the presence of this amino acid is related to NOS activity more than to ASS.…”

Section: Resultsmentioning

confidence: 97%

Liquid chromatographic–fluorimetric method for the estimation of nitric oxide biosynthesis in the central nervous system

Pérez-Neri

Montes

Boll

et al. 2004

Journal of Chromatography B

View full text Add to dashboard Cite

“…We speculate that arginase could represent a molecular mechanism that cells use to attenuate NO production and dampen inflammatory responses (27,28). That is, by upregulating arginase, cells would limit the availability of L-arg to NOS and thereby decrease NO production.…”

Section: Discussionmentioning

confidence: 99%

Cytokine-Induced Endothelial Arginase Expression Is Dependent on Epidermal Growth Factor Receptor

Nelin

Chicoine

Reber

et al. 2005

Am J Respir Cell Mol Biol

View full text Add to dashboard Cite

L-arginine is metabolized to nitric oxide (NO) by NO synthase (NOS), or to urea and L-ornithine by arginase. L-ornithine contributes to vascular remodeling in pulmonary hypertension via metabolism to polyamines and proline. Previously we found that cytokines upregulate both NOS and arginase in pulmonary arterial endothelial cells. We hypothesized that cytokine-induced arginase I and II expression depend on epidermal growth factor (EGF) receptor (EGFR) activity. Bovine pulmonary arterial endothelial cells were treated with lipopolysaccharide and tumor necrosis factor-␣ (L/T). L/T treatment resulted in a substantial increase in urea production, and this increase in urea production was potently inhibited by both genistein and AG1478, inhibitors of EGFR. Levels of arginase I protein and arginase II mRNA were increased in response to L/T treatment, and genistein prevented the L/T-induced elevations in both arginase I protein and arginase II mRNA levels. L/T treatment increased production of nitrites and inducible NOS mRNA accumulation, and genistein and AG1478 had little effect on these changes. EGF (50 ng/ml) treatment resulted in enhanced urea production. Finally, a 170-kD protein was phosphorylated upon treatment with either EGF or L/T. Our results indicate that arginase induction by L/T depends in part on EGFR activity. We speculate that EGFR inhibitors may attenuate vascular remodeling without affecting NO release, and thus may represent novel therapeutic modalities for pulmonary hypertensive disorders.

show abstract

Coinduction of Nitric Oxide Synthase and Arginine Metabolic Enzymes in Endotoxin-induced Uveitis Rats

Cited by 35 publications

References 37 publications

Therapeutic Effect of Melatonin in Experimental Uveitis

Therapeutic Effect of Melatonin in Experimental Uveitis

Liquid chromatographic–fluorimetric method for the estimation of nitric oxide biosynthesis in the central nervous system

Cytokine-Induced Endothelial Arginase Expression Is Dependent on Epidermal Growth Factor Receptor

Contact Info

Product

Resources

About