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iNOS Protein Expression (ino + protein_expression)
Selected AbstractsMolecular and histological responses in rat skin exposed to m -xylene,JOURNAL OF BIOCHEMICAL AND MOLECULAR TOXICOLOGY, Issue 2 2003Palur G. Gunasekar Abstract Solvents, surfactants, cutting fluids, hydrocarbons, and oils cause skin irritation by incompletely understood mechanisms. This study examined histological and molecular changes in rodent skin caused by brief topical exposures to m -xylene. At 0, 1, 2, 4, and 6 h after 1-h exposure, skin samples were removed and analyzed for histopathological changes and interleukin-1, (IL-1,) and inducible nitric oxide synthase (iNOS) protein levels. Histopathological changes (epidermal,dermal separation and granulocyte infiltration) and increases in IL-1, and iNOS protein expression occurred during our observation period. IL-1, levels increased by 80% immediately after exposure and iNOS levels increased about 60% 4 hours after exposure. Our study demonstrates that dermal exposure to m -xylene promotes IL-1, and iNOS production in skin and these proteins may serve as early indicators of skin irritation. © 2003 Wiley Periodicals, Inc. J Biochem Mol Toxicol 17:92,94, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/jbt.10065 [source] Acute physical exercise reverses S -nitrosation of the insulin receptor, insulin receptor substrate 1 and protein kinase B/Akt in diet-induced obese Wistar ratsTHE JOURNAL OF PHYSIOLOGY, Issue 2 2008José R. Pauli Early evidence demonstrates that exogenous nitric oxide (NO) and the NO produced by inducible nitric oxide synthase (iNOS) can induce insulin resistance. Here, we investigated whether this insulin resistance, mediated by S -nitrosation of proteins involved in early steps of the insulin signal transduction pathway, could be reversed by acute physical exercise. Rats on a high-fat diet were subjected to swimming for two 3 h-long bouts, separated by a 45 min rest period. Two or 16 h after the exercise protocol the rats were killed and proteins from the insulin signalling pathway were analysed by immunoprecipitation and immunoblotting. We demonstrated that a high-fat diet led to an increase in the iNOS protein level and S -nitrosation of insulin receptor , (IR,), insulin receptor substrate 1 (IRS1) and Akt. Interestingly, an acute bout of exercise reduced iNOS expression and S -nitrosation of proteins involved in the early steps of insulin action, and improved insulin sensitivity in diet-induced obesity rats. Furthermore, administration of GSNO (NO donor) prevents this improvement in insulin action and the use of an inhibitor of iNOS (l- N6 -(1-iminoethyl)lysine; l -NIL) simulates the effects of exercise on insulin action, insulin signalling and S -nitrosation of IR,, IRS1 and Akt. In summary, a single bout of exercise reverses insulin sensitivity in diet-induced obese rats by improving the insulin signalling pathway, in parallel with a decrease in iNOS expression and in the S -nitrosation of IR/IRS1/Akt. The decrease in iNOS protein expression in the muscle of diet-induced obese rats after an acute bout of exercise was accompanied by an increase in AMP-activated protein kinase (AMPK) activity. These results provide new insights into the mechanism by which exercise restores insulin sensitivity. [source] Expression of Inducible and Endothelial Nitric Oxide Synthases, Formation of Peroxynitrite and Reactive Oxygen Species in Human Chronic Renal Transplant FailureAMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2002Ester W. J. A. Albrecht Nitric oxide (NO·) is produced by NO synthases (NOS) and can interact with reactive oxygen species (ROS) to form peroxynitrite, which induces protein damage by formation of nitrotyrosine. NO· has a promotional effect on acute rejection. To investigate the role of NO· during chronic renal transplant failure (CRTF), we studied the expression of eNOS and iNOS in conjunction with H2O2 production and the formation of nitrotyrosines. Nephrectomy material from 10 patients and 10 control kidneys was used in this study. Expression of iNOS, eNOS, nitrotyrosine and the presence of ROS-producing cells and macrophages were determined using immunohistochemistry. INOS expression in nonsclerosed glomeruli and interstitium was significantly increased in patients with CRTF (p <,0.05). Glomerular eNOS expression was decreased in patients with CRTF compared with glomeruli of control kidneys (p <,0.01). Nitrotyrosine and ROS positive cells were significantly increased in CRTF in the interstitium (p <,0.05), but not in glomeruli. In summary, we found a marked interstitial increase in iNOS protein expression together with a decrease in glomerular eNOS expression in CRTF patients, associated with a significant increment in ROS and nitrotyrosine-positive cells in the interstitium. Our results suggest that loss of NO· production by glomerular eNOS in conjunction with an increased NO· production by interstitial iNOS, together with the formation of ROS and nitrotyrosine, is involved in the pathogenesis of CRTF. [source] Chronic inhibition of nitric-oxide synthase induces hypertension and erectile dysfunction in the rat that is not reversed by sildenafilBJU INTERNATIONAL, Issue 1 2010Serap Gur Study Type , Aetiology (case control) Level of Evidence 3b OBJECTIVE To evaluate the effect of N(G)-nitro- l -arginine methyl ester (L-NAME)-induced hypertension (HT) on erectile function in the rat and determine if the phosphodiesterase (PDE)-5 inhibitor, sildenafil, can reverse the effects of nitric oxide (NO) deficiency, as HT is a risk factor for erectile dysfunction (ED) and the NO synthase (NOS) inhibitor L-NAME induces NO-deficient HT. MATERIALS AND METHODS Thirty-six adult Sprague-Dawley male rats were divided into three groups, i.e. a control, L-NAME-HT (40 mg/rat/day in the drinking water for 4 weeks), and sildenafil-treated L-NAME-HT (1.5 mg/rat/day sildenafil, by oral gavage concomitantly with L-NAME). The erectile response expressed as a ratio of intracavernosal pressure (ICP)/mean arterial pressure (MAP), evaluated after electrical stimulation of the right cavernous nerve. The isometric tension of corpus cavernosum smooth muscle (CCSM) was measured in organ-bath experiments. NOS expression was determined immunohistochemically for neuronal (n)NOS and by Western blot analysis for endothelial (e) and inducible (i) NOS protein. cGMP levels were evaluated by enzyme-linked immunosorbent assay. RESULTS The erectile response was diminished in the HT group. Nitrergic and endothelium-dependent relaxation was reduced, while the relaxation response to sodium nitroprusside and contractile response to phenylephrine were not altered in CCSM from L-NAME-treated rats. HT rats showed decreased expression of nNOS, whereas eNOS and iNOS protein expression was increased. Sildenafil partly restored endothelial and molecular changes in CCSM from HT rats, but did not reverse the decreased erectile response, even as cGMP levels returned to normal levels. CONCLUSIONS Sildenafil treatment did not correct the ED in L-NAME-treated HT rats. Under sustained high blood pressure, up-regulation of PDE5 expression failed to reverse the depletion of neuronal NO and/or impaired nNOS activity. However, endothelium-dependent relaxation was restored. Drug targeting of neuronal dysfunction might delay the onset of ED in HT. [source] | ||||||||||