Carbon Monoxide and Nitric Oxide as Examples of the Youngest Class of Transmitters.
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ABSTRACT:
SUBMITTER: Nowaczyk A
PROVIDER: S-EPMC8199767 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:BackgroundPreeclampsia is thought to originate during placentation, with incomplete remodelling and perfusion of the spiral arteries leading to reduced placental vascular capacity. Nitric oxide (NO) and carbon monoxide (CO) are powerful vasodilators that play a role in the placental vascular system. Although family clustering of preeclampsia has been observed, the existing genetic literature is limited by a failure to consider both mother and child.MethodsWe conducted a nested case-control study within the Norwegian Mother and Child Birth Cohort of 1545 case-pairs and 995 control-pairs from 2540 validated dyads (2011 complete pairs, 529 missing mother or child genotype). We selected 1518 single-nucleotide polymorphisms (SNPs) with minor allele frequency >5% in NO and CO signalling pathways. We used log-linear Poisson regression models and likelihood ratio tests to assess maternal and child effects.ResultsOne SNP met criteria for a false discovery rate Q-value <0.05. The child variant, rs12547243 in adenylate cyclase 8 (ADCY8), was associated with an increased risk (relative risk [RR] 1.42, 95% confidence interval [CI] 1.20, 1.69 for AG vs. GG, RR 2.14, 95% CI 1.47, 3.11 for AA vs. GG, Q = 0.03). The maternal variant, rs30593 in PDE1C was associated with a decreased risk for the subtype of preeclampsia accompanied by early delivery (RR 0.45, 95% CI 0.27, 0.75 for TC vs. CC; Q = 0.02). None of the associations were replicated after correction for multiple testing.ConclusionsThis study uses a novel approach to disentangle maternal and child genotypic effects of NO and CO signalling genes on preeclampsia.
| S-EPMC5771849 | biostudies-literature
Project description:The molecular mechanisms underlying the effects of nitric oxide (NO) and carbon monoxide (CO), individually and collectively, on large-conductance calcium-activated K(+) (K(Ca)) channels were investigated in rat vascular smooth muscle cells (SMCs). Both NO and CO increased the activity of native K(Ca) channels. Dehydrosoyasaponin-I, a specific agonist for beta subunit of K(Ca) channels, increased the open probability of native K(Ca) channels only when it was delivered to the cytoplasmic surface of membrane. CO, but not NO, further increased the activity of native K(Ca) channels that had been maximally stimulated by dehydrosoyasaponin-I. After treatment of SMCs with anti-K(Ca),beta subunit antisense oligodeoxynucleotides, the stimulatory effect of NO, but not of CO, on K(Ca) channels was nullified. CO, but not NO, enhanced the K(Ca) current densities of heterologously expressed cloned K(Ca),alpha subunit, showing that the presence of K(Ca),beta subunit is not a necessity for the effect of CO but essential for that of NO. Finally, pretreatment of SMCs with NO abolished the effects of subsequently applied CO or diethyl pyrocarbonate on K(Ca) channels. In summary, the stimulatory effects of CO and NO on K(Ca) channels rely on the specific interactions of these gases with K(Ca),alpha and K(Ca),beta subunits.
| S-EPMC151105 | biostudies-literature
Project description:A decreased lung diffusing capacity for carbon monoxide (DLCO ) has been reported in a variable proportion of subjects over the first 3 months of recovery from severe coronavirus disease 2019 (COVID-19). In this study, we investigated whether measurement of lung diffusing capacity for nitric oxide (DLNO ) offers additional insights on the presence and mechanisms of gas transport abnormalities. In 94 subjects, recovering from mild-to-severe COVID-19 pneumonia, we measured DLNO and DLCO between 10 and 266 days after each patient was tested negative for severe acute respiratory syndrome coronavirus 2. In 38 subjects, a chest computed tomography (CT) was available for semiquantitative analysis at six axial levels and automatic quantitative analysis of entire lungs. DLNO was abnormal in 57% of subjects, independent of time of lung function testing and severity of COVID-19, whereas standard DLCO was reduced in only 20% and mostly within the first 3 months. These differences were not associated with changes of simultaneous DLNO /DLCO ratio, while DLCO /VA and DLNO /VA were within normal range or slightly decreased. DLCO but not DLNO positively correlated with recovery time and DLCO was within the normal range in about 90% of cases after 3 months, while DLNO was reduced in more than half of subjects. Both DLNO and DLCO inversely correlated with persisting CT ground glass opacities and mean lung attenuation, but these were more frequently associated with DLNO than DLCO decrease. These data show that an impairment of DLNO exceeding standard DLCO may be present during the recovery from COVID-19, possibly due to loss of alveolar units with alveolar membrane damage, but relatively preserved capillary volume. Alterations of gas transport may be present even in subjects who had mild COVID-19 pneumonia and no or minimal persisting CT abnormalities. TRIAL REGISTRY: ClinicalTrials.gov PRS: No.: NCT04610554 Unique Protocol ID: SARS-CoV-2_DLNO 2020.
| S-EPMC7903940 | biostudies-literature
Project description:To clarify the roles of carbon monoxide (CO), nitric oxide (NO), and auxin in the plant response to iron deficiency (-Fe), and to establish how the signaling molecules interact to enhance Fe acquisition, we conducted physiological, genetic, and molecular analyses that compared the responses of various Arabidopsis mutants, including hy1 (CO deficient), noa1 (NO deficient), nia1/nia2 (NO deficient), yuc1 (auxin over-accumulation), and cue1 (NO over-accumulation) to -Fe stress. We also generated a HY1 over-expression line (named HY1-OX) in which CO is over-produced compared to wild-type. We found that the suppression of CO and NO generation using various inhibitors enhanced the sensitivity of wild-type plants to Fe depletion. Similarly, the hy1, noa1, and nia1/nia2 mutants were more sensitive to Fe deficiency. By contrast, the yuc1, cue1, and HY1-OX lines were less sensitive to Fe depletion. The hy1 mutant with low CO content exhibited no induced expression of the Fe uptake-related genes FIT1 and FRO2 as compared to wild-type plants. On the other hand, the treatments of exogenous CO and NO enhanced Fe uptake. Likewise, cue1 and HY1-OX lines with increased endogenous content of NO and CO, respectively, also exhibited enhanced Fe uptake and increased expression of bHLH transcriptional factor FIT1as compared to wild-type plants. Furthermore, we found that CO affected auxin accumulation and transport in the root tip by altering the PIN1 and PIN2 proteins distribution that control lateral root structure under -Fe stress. Our results demonstrated the integration of CO, NO, and auxin signaling to cope with Fe deficiency in Arabidopsis.
| S-EPMC4780267 | biostudies-literature
Project description:Carbon monoxide (CO) has emerged as a vascular homeostatic molecule that prevents balloon angioplasty-induced stenosis via antiproliferative effects on vascular smooth muscle cells. The effects of CO on reendothelialization have not been evaluated.Exposure to CO has diametrically opposite effects on endothelial cell (EC) and vascular smooth muscle cell proliferation in rodent models of carotid injury. In contrast to its effect of blocking vascular smooth muscle cell growth, CO administered as a gas or as a CO-releasing molecule enhances proliferation and motility of ECs in vitro by >50% versus air controls, and in vivo, it accelerates reendothelialization of the denuded artery by day 4 after injury versus day 6 in air-treated animals. CO enhanced EC proliferation via rapid activation of RhoA (Ras homolog gene family, member A), followed by downstream phosphorylation of Akt, endothelial nitric oxide (NO) synthase phosphorylation, and a 60% increase in NO generation by ECs. CO drives cell cycle progression through phosphorylation of retinoblastoma, which is dependent in part on endothelial NO synthase-generated NO. Similarly, endothelial repair in vivo requires NO-dependent mobilization of bone marrow-derived EC progenitors, and CO yielded a 4-fold increase in the number of mobilized green fluorescent protein-Tie2-positive endothelial progenitor cells versus controls, with a corresponding accelerated deposition of differentiated green fluorescent protein-Tie2-positive ECs at the site of injury. CO was ineffective in augmenting EC repair and the ensuing development of intimal hyperplasia in eNOS(-/-) mice.Collectively, the present data demonstrate that CO accelerates EC proliferation and vessel repair in a manner dependent on NO generation and enhanced recruitment of bone marrow-derived endothelial progenitor cells.
| S-EPMC2841354 | biostudies-literature
Project description:Exhaled carbon monoxide (eCO) and fractional exhaled nitric oxide (FeNO) could reflect underlying inflammatory and oxidative stresses, which play important roles in pathogenetic pathways of metabolic syndrome (MetS). However, epidemiologic evidence was limited. We conducted a study in Wuhan-Zhuhai (WHZH) cohort of 3649 community participants to investigate the association between eCO, FeNO and MetS in both cross-sectional and prospective ways. The results showed that higher eCO and FeNO were associated cross-sectionally with a higher prevalence of MetS. The multivariable-adjusted odds ratios for MetS at baseline were 1.22 (95% confidence interval [CI]: 1.11 to 1.35) associated with per log eCO and 1.14 (95% CI: 1.00 to 1.30) associated with per log FeNO. During a follow-up of 3 years, 358/2181 new developed MetS cases were identified. Compared with lowest quartile of eCO and FeNO, the multivariable-adjusted risk ratios (95% CI) for MetS were 1.48 (1.06 to 2.06) related to the highest quartile of eCO. These findings remained consistent across sex but not smoking status, eCO was only associated with MetS in non-smokers when stratified by smoking status. In conclusion, our study demonstrated that eCO and FeNO were independently and positively associated with the prevalence of MetS cross-sectionally, while only eCO was positively related with the incidence of MetS prospectively.
| S-EPMC4830973 | biostudies-literature
Project description:Greening of etiolated plants is predominantly stimulated by light but the complete molecular mechanism is still unknown. Multiple studies currently focus on the important physiological effects of heme oxygenase (HO)/carbon monoxide (CO) in plants. In this report, firstly, the role of HO/CO in light-induced de-etiolation process was investigated. We discovered that light could significantly increase HO activities, HO-1 gene expression, CO release, and chlorophyll accumulation, all of which were sensitive to zinc protoporphyrin (ZnPPIX), the potent inhibitor of HO-1, respectively. Both HO-1 inducer hematin (H) and CO aqueous solution were able to relieve etiolation in wheat seedling leaves under completely darkness by up-regulating endogenous HO/CO system, so as nitric oxide (NO) donor sodium nitroprusside (SNP) did. Similarly, endogenous NO production was also boost in response to light, SNP, hematin and CO aqueous solution in wheat seedling leaves. Additionally, the restoration of chlorophyll contents was blocked, when the inhibitor of mammalian nitric oxide synthase N(G)-nitro-L-arginine methylester hydrochloride (L-NAME) or the specific scavenger of NO 2-(4-carboxyphenyl)-4, 4, 5, 5-tetramethylimidazoline-1-oxyl-3-oxide potassium salt (cPTIO) was added, respectively. Furthermore, the inducible effects of light were different from those of SNP, hematin, and CO on Pfr accumulation and PHYA transcripts. However, all of sodium nitroprusside (SNP), hematin, and CO could accelerate NO emission, which suggested that HO/CO in wheat seedlings de-etiolation under dark-light transition may have a cross talk with NO.
| S-EPMC3861272 | biostudies-literature
Project description:Carbon monoxide (CO) is an endogenous gaseous molecule in organisms. Despite its reputation as a lethal gas, recent studies have shown that it is one of the most essential cellular components regulating a variety of biological processes. However, whether CO regulates physiological processes of morphological or developmental patterns in plants is largely unknown. In this paper, the observation that exogenous CO was able to promote the formation of tomato lateral roots (LR) is described. The CO stimulation of LR development was supported by analysis of tomato haem oxygenase-1 (LeHO-1), an enzymatic source of intracellular CO. It is shown that the amount of LeHO-1 proteins and transcripts increased parallel to the LR development. In addition, LeHO-1 loss-of-function tomato mutant yg-2 showed a phenotype of impaired LR development. The phenotype of yg-2 could be restored by treatment with CO. Since auxin is required for LR initiation and NO is shown to be a mediator for LR development, the correlation of CO with auxin and NO was tested. Our analysis revealed that the action of CO was blocked by the auxin transport inhibitor N-1-naphthylphthalamic acid and the NO scavenger cPTIO, respectively. Furthermore, the whole seedling assays of IAA show that treatment with CO increased the overall IAA levels in various tissues of tomato. Exposure of tomato roots to CO also enhanced intracellular NO generation. These results indicate that CO plays a critical role in controlling architectural change in tomato roots.
| S-EPMC2529230 | biostudies-literature
Project description:Carbon monoxide (CO), generated by heme oxygenase (HO), has been considered a signaling molecule in both the cardiovascular and central nervous systems. The biological function of the HO/CO axis is mostly related to other gaseous molecules, including nitric oxide (NO), which is synthesized by nitric oxide synthase (NOS). Healthy blood vessels are essential for the maintenance of tissue homeostasis and whole-body metabolism; however, decreased or impaired vascular function is a high-risk factor of cardiovascular and neuronal diseases. Accumulating evidence supports that the interplay between CO and NO plays a crucial role in vascular homeostasis and regeneration by improving endothelial function. Moreover, endothelial cells communicate with neighboring cells, such as, smooth muscle cells, immune cells, pericytes, and astrocytes in the periphery and neuronal vascular systems. Endogenous CO could mediate the cell-cell communication and improve the physiological functions of the cardiovascular and neurovascular systems via crosstalk with NO. Thus, a forward, positive feedback circuit between HO/CO and NOS/NO pathways can maintain cardiovascular and neurovascular homeostasis and prevent various human diseases. We discussed the crucial role of CO-NO crosstalk in the cardiovascular and neurovascular systems.
| S-EPMC8071856 | biostudies-literature
Project description:A hemolysis-linked subphenotype of sickle cell disease (SCD), characterized by pulmonary hypertension, stroke, priapism and leg ulcers, is associated with decreased nitric oxide bioavailability and vasculopathy. Vasculopathy appears to have a multifactorial etiology, including mechanisms primarily that involve deficient nitric oxide (NO) signaling, but also involving altered function of NO synthase related to substrate availability and cooperating factors such as apolipoproteins. Improved understanding of the vascular pathophysiology of SCD has led to new vascular targets for translational research in SCD. This growing vascular therapeutics field in SCD is complementary to the ongoing efforts to reduce the morbidity of vaso-occlusive pain crisis. This presentation will review the current biology and translational clinical development of novel small molecules targeting sickle cell vasculopathy. Strategies targeting the hemeoxygenase-carbon monoxide pathway, the arginine-NO synthase-cGMP-phosphodiesterase 5 pathway, the nitrate-nitrite-NO pathway, and the apolipoprotein A-I pathways will be reviewed. In this context, current clinical trials of inhaled NO, CO, nitrite, sildenafil and apoA-I mimetics will be discussed.
| S-EPMC2778246 | biostudies-literature