Variation of genes involved in oxidative and nitrosative stresses in depression

2018 ◽  
Vol 48 (1) ◽  
pp. 38-48 ◽  
Author(s):  
Paulina Wigner ◽  
Piotr Czarny ◽  
Ewelina Synowiec ◽  
Micha� Bijak ◽  
Katarzyna Białek ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Depressive Disorders ◽  
Nitrosative Stress ◽  
Nucleotide Polymorphisms ◽  
Oxidative And Nitrosative Stress ◽  
Increased Risk ◽  
Genes Encoding ◽  
Oxide Synthase ◽  
The Impact

AbstractThe dominating hypothesis among numerous hypotheses explaining the pathogenesis of depressive disorders (DD) is the one involving oxidative and nitrosative stress. In this study, we examined the association between single-nucleotide polymorphisms of the genes encoding SOD2 (superoxide dismutase 2), CAT (catalase), GPx4 (glutathione peroxidase 4), NOS1 (nitric oxide synthase 1), NOS2 (nitric oxide synthase 2), and the development of depressive disorders. Our study was carried out on the DNA isolated from peripheral blood collected from 281 depressed patients and 229 controls. Using TaqMan probes, we genotyped the following six polymorphisms: c.47T > C (p.Val16Ala) (rs4880) in SOD2, c.-89A > T (rs7943316) in CAT, c.660T > C (rs713041) in GPx4, c.-420-34221G > A (rs1879417) in NOS1, c.1823C > T (p.Ser608Leu) (rs2297518), and c.-227G > C (rs10459953) in NOS2. We found that the T/T genotype of the c.47T > C polymorphism was linked with an increased risk of depression. Moreover, the T/T genotype and T allele of c.660T > C increased the risk of DD occurrence, while the heterozygote and C allele decreased this risk. On the other hand, we discovered that the A/A genotype of c.-89A > T SNP was associated with a reduced risk of DD, while the A/T genotype increased this risk. We did not find any correlation between the genotypes/alleles of c.-420-34221G > A, c.1823C > T, and c.-227G > C, and the occurrence of DD. In addition, gene-gene and haplotype analyses revealed that combined genotypes and haplotypes were connected with the disease. Moreover, we found that sex influenced the impact of some SNPs on the risk of depression. Concluding, the studied polymorphisms of SOD2, CAT and GPx4 may modulate the risk of depression. These results support the hypothesis that oxidative and nitrosative stresses are involved in the pathogenesis of depressive disorders.

Sex differences in nitrosative stress during renal ischemia

2010 ◽  
Vol 299 (5) ◽  
pp. R1387-R1395 ◽  
Author(s):  
Francisca Rodríguez ◽  
Susana Nieto-Cerón ◽  
Francisco J. Fenoy ◽  
Bernardo López ◽  
Isabel Hernández ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Sex Differences ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Differential Pulse ◽  
Sprague Dawley ◽  
Oxidative And Nitrosative Stress ◽  
Sprague Dawley Rats ◽  
Oxide Synthase ◽  
Endothelial Nitric Oxide

Females. suffer a less severe ischemic acute renal failure than males, apparently because of higher nitric oxide (NO) bioavailability and/or lower levels of oxidative stress. Because the renal ischemic injury is associated with outer medullary (OM) endothelial dysfunction, the present study evaluated sex differences in OM changes of NO and peroxynitrite levels (by differential pulse voltammetry and amperometry, respectively) during 45 min of ischemia and 60 min of reperfusion in anesthetized Sprague-Dawley rats. Endothelial nitric oxide synthase (eNOS) and neuronal nitric oxide synthase (nNOS) protein expression and their phosphorylated forms [peNOS(Ser1177) and pnNOS(Ser1417)], 3-nitrotyrosine, reduced sulfhydryl groups (-SH), and glomerular filtration rate (GFR) were also determined. No sex differences were observed in monomeric eNOS and nNOS expression, NO, or 3-nitrotyrosine levels in nonischemic kidneys, but renal -SH content was higher in females. Ischemia increased dimeric/monomeric eNOS and nNOS ratio more in females, but the dimeric phosphorylated peNOS(Ser1177) and pnNOS(Ser1417) forms rose similarly in both sexes, indicating no sex differences in nitric oxide synthase activation. However, NO levels increased more in females than in males (6,406.0 ± 742.5 and 4,058.2 ± 272.35 nmol/l respectively, P < 0.05), together with a lower increase in peroxynitrite current (5.5 ± 0.7 vs. 12.7 ± 1.5 nA, P < 0.05) and 3-nitrotyrosine concentration, (28.7 ± 3.7 vs. 48.7 ± 3.7 nmol/mg protein, P < 0.05) in females than in males and a better preserved GFR after ischemia in females than in males (689.7 ± 135.0 and 221.4 ± 52.5 μl·min−1·g kidney wt−1, P < 0.01). Pretreatment with the antioxidants N-acetyl-l-cysteine or ebselen abolished sex differences in peroxynitrite, nitrotyrosine, and GFR, suggesting that a greater oxidative and nitrosative stress worsens renal damage in males.

Stimulation of the endogenous hydrogen sulfide synthesis suppresses oxidative–nitrosative stress and restores endothelial-dependent vasorelaxation in old rats

2020 ◽  
Vol 98 (5) ◽  
pp. 275-281 ◽  
Author(s):  
L.A. Mys ◽  
N.A. Strutynska ◽  
Y.V. Goshovska ◽  
V.F. Sagach
Keyword(s):  
Nitric Oxide ◽  
Hydrogen Sulfide ◽  
Nitric Oxide Synthase ◽  
Vascular Reactivity ◽  
Nitrosative Stress ◽  
Rat Aorta ◽  
Aortic Tissue ◽  
Old Rats ◽  
Oxide Synthase ◽  
Stimulation Of

Hydrogen sulfide (H2S) is an endogenous gas transmitter with profound effects on the cardiovascular system. We hypothesized that stimulation of H2S synthesis might alleviate age-associated changes in vascular reactivity. Pyridoxal-5-phosphate (PLP), the coenzyme of H2S-synthesizing enzymes, was administrated to old male Wistar rats per os at a dose of 0.7 mg/kg body mass once a day for 2 weeks. H2S content in the aortic tissue, markers of oxidative stress, inducible nitric oxide synthase (iNOS) and constitutive nitric oxide synthase (cNOS), arginase activities, and endothelium-dependent vasorelaxation of the aortic rings were studied. Our results showed that PLP restored endogenous H2S and low molecular weight S-nitrosothiol levels in old rat aorta to the levels detected in adults. PLP significantly reduced diene conjugate content, hydrogen peroxide and peroxynitrite generation rates, and iNOS and arginase activity in the aortic tissue of old rats. PLP also greatly improved acetylcholine-induced relaxation of old rat aorta (47.7% ± 4.8% versus 18.4% ± 4.1% in old rats, P < 0.05) that was abolished by NO inhibition with N-nitro-l-arginine methyl ester hydrochloride (L-NAME) or H2S inhibition with O-carboxymethylhydroxylamine (O-CMH). Thus, PLP might be used for stimulation of endogenous H2S synthesis and correction of oxidative and nitrosative stress and vessel tone dysfunction in aging and age-associated diseases.

Renoprotective and antihypertensive effects of S-allylcysteine in 5/6 nephrectomized rats

2007 ◽  
Vol 293 (5) ◽  
pp. F1691-F1698 ◽  
Author(s):  
Cristino Cruz ◽  
Ricardo Correa-Rotter ◽  
Dolores Javier Sánchez-González ◽  
Rogelio Hernández-Pando ◽  
Perla D. Maldonado ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Inducible Nitric Oxide Synthase ◽  
Renal Damage ◽  
Nitrosative Stress ◽  
Antioxidant Properties ◽  
Oxidative And Nitrosative Stress ◽  
Nitric Oxide Synthase 3 ◽  
Oxide Synthase ◽  
Inducible Nitric Oxide

Progressive renal damage and hypertension are associated with oxidative and nitrosative stress. On the other hand, S-allylcysteine (SAC), the most abundant organosulfur compound in aged garlic extract (AG), has antioxidant properties. The effects of SAC and AG on blood pressure, renal damage, and oxidative and nitrosative stress were studied in five-sixths nephrectomized rats treated with SAC (200 mg/kg ip) and AG (1.2 ml/kg ip) every other day for 30 days. Proteinuria and serum creatinine and blood urea nitrogen concentrations were measured on days 0, 5, 10, 15, and 30, and systolic blood pressure was recorded on days 0, 15, and 30. The degree of glomerulosclerosis and tubulointerstitial damage, the immunostaining for inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), and the subunits of NADPH oxidase p22phox and gp91phox, and the activity of SOD were determined on day 30. SAC and AG reduced hypertension, renal damage, and the abundance of inducible nitric oxide synthase, 3-nitrotyrosine, poly(ADP-ribose), p22phox, and gp91phox and increased SOD activity. Our data suggest that the antihypertensive and renoprotective effects of SAC and AG are associated with their antioxidant properties and that they may be used to ameliorate hypertension and delay the progression of renal damage.

scholarly journals Nitric oxide produced by periostial hemocytes modulates the bacterial infection-induced reduction of the mosquito heart rate

2020 ◽  
Vol 223 (15) ◽  
pp. jeb225821
Author(s):  
Tania Y. Estévez-Lao ◽  
Leah T. Sigle ◽  
Scherly N. Gomez ◽  
Julián F. Hillyer
Keyword(s):  
Nitric Oxide ◽  
Heart Rate ◽  
Nitric Oxide Synthase ◽  
Bacterial Infection ◽  
Micrococcus Luteus ◽  
Cardiac Phenotype ◽  
Expression Of Genes ◽  
Genes Encoding ◽  
Neuropeptide F ◽  
Oxide Synthase

ABSTRACTThe circulatory and immune systems of mosquitoes are functionally integrated. An infection induces the migration of hemocytes to the dorsal vessel, and specifically, to the regions surrounding the ostia of the heart. These periostial hemocytes phagocytose pathogens in the areas of the hemocoel that experience the highest hemolymph flow. Here, we investigated whether a bacterial infection affects cardiac rhythmicity in the African malaria mosquito, Anopheles gambiae. We discovered that infection with Escherichia coli, Staphylococcus aureus and Staphylococcus epidermidis, but not Micrococcus luteus, reduces the mosquito heart rate and alters the proportional directionality of heart contractions. Infection does not alter the expression of genes encoding crustacean cardioactive peptide (CCAP), FMRFamide, corazonin, neuropeptide F or short neuropeptide F, indicating that they do not drive the cardiac phenotype. Infection upregulates the transcription of two superoxide dismutase (SOD) genes, catalase and a glutathione peroxidase, but dramatically induces upregulation of nitric oxide synthase (NOS) in both the heart and hemocytes. Within the heart, nitric oxide synthase is produced by periostial hemocytes, and chemically inhibiting the production of nitric oxide using l-NAME reverses the infection-induced cardiac phenotype. Finally, infection induces the upregulation of two lysozyme genes in the heart and other tissues, and treating mosquitoes with lysozyme reduces the heart rate in a manner reminiscent of the infection phenotype. These data demonstrate an exciting new facet of the integration between the immune and circulatory systems of insects, whereby a hemocyte-produced factor with immune activity, namely nitric oxide, modulates heart physiology.

Early Recruitment of Cerebral Microcirculation by Neuronal Nitric Oxide Synthase Inhibition in a Juvenile Ischemic Rat Model

2015 ◽  
Vol 41 (1-2) ◽  
pp. 40-49 ◽  
Author(s):  
P.L. Leger ◽  
P. Bonnin ◽  
R. Moretti ◽  
S. Tanaka ◽  
J. Duranteau ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Ischemia Reperfusion ◽  
Neuronal Nitric Oxide Synthase ◽  
Dark Field ◽  
Laser Speckle ◽  
Arterial Blood Flow ◽  
Collateral Flow ◽  
Oxide Synthase ◽  
The Impact

Background: The development of collateral circulation is proposed as an inherent compensatory mechanism to restore impaired blood perfusion after ischemia, at least in the penumbra. We have studied the dynamic macro- and microcirculation after ischemia-reperfusion in the juvenile rat brain and evaluated the impact of neuronal nitric oxide synthase (nNOS) inhibition on the collateral flow. Methods: Fourteen-day-old (P14) rats were subjected to ischemia-reperfusion and treated with either PBS or 7-nitroindazole (7-NI, an nNOS inhibitor, 25 mg/kg). Arterial blood flow (BF) was measured using 2D-color-coded pulsed ultrasound imaging. Laser speckle contrast (LSC) imaging and sidestream dark-field videomicroscopy were used to measure cortical and microvascular BF, respectively. Results: In basal conditions, 7-NI reduced BF in the internal carotids (by ∼25%) and cortical (by ∼30%) BF, as compared to PBS. During ischemia, the increased mean BF velocity in the basilar trunk after both PBS and 7-NI demonstrated the establishment of collateral support and patency. Upon re-flow, BF immediately recovered to basal values in the internal carotid arteries under both conditions. The 7-NI group showed increased collateral flow in the penumbral tissue during early re-flow compared to PBS, as shown with both LSC imaging and side-stream dark-field videomicroscopy. The proportion of perfused capillaries was significantly increased under 7-NI as compared to PBS when given before ischemia (67.0 ± 3.9 vs. 46.8 ± 8.8, p < 0.01). Perfused capillaries (63.1 ± 17.7 vs. 81.1 ± 20.7, p < 0.001) and the BF index (2.4 ± 0.6 vs. 1.3 ± 0.1, p < 0.001) significantly increased under 7-NI given at the re-flow onset. Conclusions: Collateral support in the penumbra is initiated during ischemia, and may be increased during early re-flow by neuronal NOS inhibition (given in pre- and post-treatment), which may preserve brain tissue in juvenile rats.

Nitric oxide synthase and oxidative-nitrosative stress play a key role in placental infection byTrypanosoma cruzi

2018 ◽  
Vol 80 (1) ◽  
pp. e12852 ◽  
Author(s):  
María Fernanda Triquell ◽  
Cintia Díaz-Luján ◽  
María Cristina Romanini ◽  
Juan Carlos Ramirez ◽  
Patricia Paglini-Oliva ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Nitric Oxide Synthase ◽  
Nitrosative Stress ◽  
Placental Infection ◽  
Oxide Synthase

Oxidative and nitrosative stress in acute renal ischemia

2001 ◽  
Vol 281 (5) ◽  
pp. F948-F957 ◽  
Author(s):  
Eisei Noiri ◽  
Akihide Nakao ◽  
Koji Uchida ◽  
Hirokazu Tsukahara ◽  
Minoru Ohno ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Lipid Peroxidation ◽  
Dna Damage ◽  
Oxidative Dna Damage ◽  
Nitrosative Stress ◽  
Oxidative And Nitrosative Stress ◽  
Reperfusion Period ◽  
Series Of Experiments ◽  
Acute Renal Ischemia ◽  
Oxide Synthase

First Published July 12, 2001; 10.1152/ajprenal.0071.2001.—Generation of reactive oxygen species and nitric oxide in hypoxia-reperfusion injury may form a cytotoxic metabolite, peroxynitrite, which is capable of causing lipid peroxidation and DNA damage. This study was designed to examine the contribution of oxidative and nitrosative stress to the renal damage in ischemic acute renal failure (iARF). iARF was initiated in rats by 45-min renal artery clamping. This resulted in lipid peroxidation, DNA damage, and nitrotyrosine modification confirmed both by Western and immunohistochemical analyses. Three groups of animals were randomly treated with an inhibitor of inducible nitric oxide synthase (NOS),l- N 6-(1-iminoethyl)lysine (l-Nil), cell-permeable lecithinized superoxide dismutase (SOD), or both. Each treatment resulted in amelioration of renal dysfunction, as well as reduced nitrotyrosine formation, lipid peroxidation, and DNA damage, thus suggesting that peroxynitrite rather than superoxide anion is responsible for lipid peroxidation and DNA damage. Therefore, in a separate series of experiments, a scavenger of peroxynitrite, ebselen, was administered before the reperfusion period. This treatment resulted in a comparable degree of amelioration of iARF. In conclusion, the present study provides the first attempt to elucidate the role of peroxynitrite in initiation of the cascade of lipid peroxidation and DNA damage to ischemic kidneys. The results demonstrate that l-Nil , lecithinized SOD, and ebselen treatments improve renal function due to their suppression of peroxynitrite production or its scavenging, consequently preventing lipid peroxidation and oxidative DNA damage.

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