Disease relevance of NOS2A

• Incubation of BAECs with IL-1 beta-prestimulated BVSMCs induced EC toxicity, which was partially inhibited by an inhibitor of NO synthesis, NG-nitro-L-arginine methyl ester, or an inhibitor of iNOS expression, dexamethasone [1].
• Inasmuch as aminoguanidine is a relatively selective inhibitor of the inducible isoform of nitric oxide synthase (iNOS), we have investigated the effects of hyperglycemia on the retinal nitric oxide (NO) pathway in the presence and absence of aminoguanidine [2].
• The pancreatic responses in AM and iNOS may play a major role in mediating prolonged disturbances in nutrient use by tissues through their influences on temporal patterns of pancreatic hormone secretion during chronic illness [3].
• BACKGROUND: Inflammatory related cardiovascular disease, i.e. cardiac allograft rejection, myocarditis, septic shock, are accompanied by cytokine production, which stimulates the expression of inducible nitric oxide (iNOS) [4].
• We assessed the kinetics of inducible nitric oxide synthase (iNOS) mRNA expression and production of nitric oxide (NO) in bovine alveolar macrophages (AMs) stimulated with purified lipopolysaccharide (LPS) from Pasteurella haemolytica strain 12296 [5].

Psychiatry related information on NOS2A

• LPS increased CAT-2 mRNA after LPS; GH was associated with a 24% reduction in CAT-2 mRNA content at the peak time response. cNOS activity was 3-fold greater than iNOS after LPS [6].

High impact information on NOS2A

• These results indicate that single irradiation does not affect Ca(2+) mobilization and eNOS expression but induces the expression of iNOS in BAECs, and the latter property would be beneficial to induce apoptosis in the adjacent tumor cells [7].
• RESULTS: MSU induced MMP-3 and iNOS expression and NO release in chondrocytes in a p38-dependent manner that did not require interleukin-1 (IL-1), as demonstrated by using IL-1 receptor antagonist [8].
• CONCLUSION: These findings support the hypothesis that a component of S. aureus can stimulate iNOS in articular cartilage, and that NO generated from this enzyme down-regulates cartilage matrix proteoglycan synthesis [9].
• Bovine retinal pigmented epithelial cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon-gamma (IFN-gamma) and lipopolysaccharide (LPS) [10].
• SB 203580 did not inhibit iNOS activity, as measured by the conversion of arginine to citrulline, when added directly to cultures where the enzyme had already been induced, but had to be present during the induction period [11].

Chemical compound and disease context of NOS2A

• CONCLUSION: Inhibition of iNOS in articular chondrocytes may be a new mechanism by which minocycline could exert its beneficial effects in the treatment of joint diseases [12].
• As part of this inquiry, we stably transduced a NOS-2 encoding retrovirus into endothelial cells cultured on Gelfoam blocks in the absence of penicillin G [13].
• Heat-killed Listeria monocytogenes induced more iNOS mRNA and nitrite than IFN-gamma, but much less than L. mono-cytogenes and IFN-gamma combined [14].

Biological context of NOS2A

• The presence of IFN-alpha or IFN-beta did not accelerate mRNA degradation, implying that these interferons did not affect NOS-2 mRNA stability, but more probably NOS-2 gene expression [15].
• Massive production of NO after inducible NO synthase (iNOS) expression has been implicated in cell death [16].
• Inhibition of iNOS gene expression was measured by Northern blot analysis in IL-1alpha-stimulated, cartilage-derived chondrocytes [17].
• These findings suggest that the use of iNOS gene therapy for pulmonary hypertensive disorders may not only be beneficial through NO-mediated pulmonary vasodilation but also may decrease vascular remodeling by limiting L-Orn production by native arginase [18].
• The mRNA expression for iNOS decreased (P < 0.05) after induction of luteolysis [19].

Anatomical context of NOS2A

• Immunoreactive iNOS protein was localised in secretory epithelial cells as well as in the lamina muscularis [20].
• By in situ hybridisation, specific iNOS transcripts were additionally demonstrated in the oviduct epithelium [20].
• Northern blot analysis revealed increased iNOS mRNA expression in bovine chondrocytes in response to denatured S. aureus stimulation [9].
• Fibroblast growth factor-2 (FGF-2) inhibited LPS-IFN-gamma-induced nitrite release and NOS-2 messenger RNA accumulation in keratocytes but not in BCE cells [21].
• These acute complications rapidly progress into a more chronic state characterized by diminished insulin response to feeding stimulus and colocalized increases in pancreatic islet AM and iNOS [3].

Associations of NOS2A with chemical compounds

• Bovine retinal pigmented epithelial (RPE) cells express an inducible nitric oxide synthase (NOS-2) after activation with interferon (IFN)-gamma and lipopolysaccharide (LPS) [15].
• Using a 372-bp probe for bovine iNOS we demonstrated inhibition of IL-1-induced mRNA by SB 203580 at both 4 and 24 h following IL-1 treatment [11].
• METHODS: Nitric oxide (NO) release, and expression of inducible nitric oxide synthase (iNOS) and matrix metalloproteinase 3 (MMP-3) were assessed in cultured chondrocytes treated with MSU [8].
• Induction of iNOS with subsequent peroxynitrite formation may contribute to bovine cerebral EC death caused by OGD [16].
• The involvement of iNOS in EC death was suggested by partial reduction of cell death by NO synthase inhibitors, including L-N(G)-(1-iminoethyl)ornithine and nitro-L-arginine, and an NO scavenger, the Fe(2+)-N-methyl-D-glucamine dithiocarbamate complex [16].

Regulatory relationships of NOS2A

• We conclude that although TNF alpha is able to stimulate cGMP formation in theca cells by inducing the expression of inducible NOS, the mechanism underlying the TNF alpha-mediated inhibition of LH-stimulated prorenin production is independent of its ability to induce cGMP formation [22].

Other interactions of NOS2A

• Taken together, our data suggest that the transcriptional inducible NOS response to OCP crystals involved both the p38 and the JNK MAPK pathways, probably under the control of activator protein-1 [23].
• Real-time PCR and Western blotting techniques established the presence of the three known nitric oxide synthases in cerebral endothelial cells: NOS-1 (neuronal), NOS-2 (inducible), and NOS-3 (endothelial) [24].

Analytical, diagnostic and therapeutic context of NOS2A

• In addition, eNOS and iNOS mRNA and protein were localised by in situ hybridisation and immunocytochemistry respectively [20].
• Inducible NO synthase (iNOS) messenger RNA (mRNA) expression was analyzed by Northern blot [9].
• The iNOS mRNA levels were consistent with NO levels in 24-h cell culture supernatants of the IL-1-stimulated bovine chondrocytes used to obtain the RNA [11].
• In vivo iNOS expression by WF was confirmed by in situ hybridization and immunohistochemistry [25].
• This effect was accompanied by reduced expression of inducible NO synthase (iNOS) in BVSMCs coincubated with BAECs, as analyzed by Western blot analysis [1].

References