Endogenous Nitric Oxide Levels Research Articles

Ethylene Renders Silver Nanoparticles Stress Tolerance in Rice Seedlings by Regulating Endogenous Nitric Oxide Accumulation.

Developments in the field of nanotechnology over the past few years have increased the prevalence of silver nanoparticles (AgNPs) in the environment, resulting in increased exposure of plants to AgNPs. Recently, various studies have reported the effect of AgNPs on plant growth at different concentrations. However, identifying the mechanisms and signaling molecules involved in plant responses against AgNPs stress is crucial to find an effective way to deal with the phytotoxic impacts of AgNPs on plant growth and development. Therefore, this study was envisaged to investigate the participation of ethylene in mediating the activation of AgNPs stress tolerance in rice (Oryza sativa L.) through a switch that regulates endogenous nitric oxide (NO) accumulation. Treatment of AgNPs alone hampered the growth of rice seedlings due to severe oxidative stress as a result of decline in sulfur assimilation, glutathione (GSH) biosynthesis and alteration in the redox status of GSH. These results are also accompanied by the higher endogenous NO level. However, addition of ethephon (a donor of ethylene) reversed the AgNP-induced effects. Though the application of silicon nanoparticles (SiNPs) alone promoted the growth of rice seedlings but, interestingly their application in combination with AgNPs enhanced the AgNP-induced toxicity in the seedlings through the same routes as exhibited in the case of AgNPs alone treatment. Interestingly, addition of ethephon reversed the negative effects of SiNPs under AgNPs stress. These results suggest that ethylene might act as a switch to regulate the level of endogenous NO, which in turn could be associated with AgNPs stress tolerance in rice. Furthermore, the results also indicated that addition of l-NG-nitro arginine methyl ester (l-NAME) (an inhibitor of endogenous NO synthesis) also reversed the toxic effects of SiNPs together with AgNPs, further suggesting that the low level of endogenous NO was associated with AgNPs stress tolerance. Overall, the results indicate that the low level of endogenous NO triggers AgNPs stress tolerance, while high level leads to AgNPs toxicity by regulating sulfur assimilation, GSH biosynthesis, redox status of GSH and oxidative stress markers. The results revealed that ethylene might act as a switch for regulating AgNPs stress in rice seedlings by controlling endogenous NO accumulation.

Nitric oxide alleviates salt stress through protein S-nitrosylation and transcriptional regulation in tomato seedlings.

NO enhances the resistance of tomato seedlings to salt stress through protein S-nitrosylation and transcriptional regulation, which involves the regulation of MAPK signaling and carbohydrate metabolism. Nitric oxide (NO) regulates various physiological and biochemical processes and stress responses in plants. We found that S-nitrosoglutathione (GSNO) treatment significantly promoted the growth of tomato seedling under NaCl stress, indicating that NO plays a positive role in salt stress resistance. Moreover, GSNO pretreatment resulted in an increase of endogenous NO level, S-nitrosothiol (SNO) content, S-nitrosoglutathione reductase (GSNOR) activity and GSNOR expression under salt stress, implicating that S-nitrosylation might be involved in NO-alleviating salt stress. To further explore whether S-nitrosylation is a key molecular mechanism of NO-alleviating salt stress, the biotin-switch technique and liquid chromatography/mass spectrometry/mass spectrometry (LC-MS/MS) were conducted. Atotal of 1054 putative S-nitrosylated proteins have been identified, which were mainly enriched in chloroplast, cytoplasm and mitochondrion. Among them, 15 and 22 S-nitrosylated proteins were involved in mitogen-activated protein kinase (MAPK) signal transduction and carbohydrate metabolism, respectively. In MAPK signaling, various S-nitrosylated proteins, SAM1, SAM3, SAM, PP2C and SnRK, were down-regulated and MAPK, MAPKK and MAPKK5 were up-regulated at the transcriptional level by GSNO treatment under salt stress compared to NaCl treatment alone. The GSNO pretreatment could reduce ethylene production and ABA content under NaCl stress. In addition, the activities of enzyme identified in carbohydrate metabolism, their expression at the transcriptional level and the metabolite content were up-regulated by GSNO supplication under salt stress, resulting in the activation of glycolysis and tricarboxylic acid cycle (TCA) cycles. Thus, these results demonstrated that NO might beneficially regulate MAPK signaling at transcriptional levels and activate carbohydrate metabolism at the post-translational and transcriptional level, protecting seedlings from energy deficiency and salinity, thereby alleviating salt stress-induced damage in tomato seedlings. It provides initial insights into the regulatory mechanisms of NO in response to salt stress.

The Role of Nitric Oxide Signaling in Plant Responses to Cadmium Stress.

Nitric oxide (NO) is a widely distributed gaseous signaling molecule in plants that can be synthesized through enzymatic and non-enzymatic pathways and plays an important role in plant growth and development, signal transduction, and response to biotic and abiotic stresses. Cadmium (Cd) is a heavy metal pollutant widely found in the environment, which not only inhibits plant growth but also enters humans through the food chain and endangers human health. To reduce or avoid the adverse effects of Cd stress, plants have evolved a range of coping mechanisms. Many studies have shown that NO is also involved in the plant response to Cd stress and plays an important role in regulating the resistance of plants to Cd stress. However, until now, the mechanisms by which Cd stress regulates the level of endogenous NO accumulation in plant cells remained unclear, and the role of exogenous NO in plant responses to Cd stress is controversial. This review describes the pathways of NO production in plants, the changes in endogenous NO levels in plants under Cd stress, and the effects of exogenous NO on regulating plant resistance to Cd stress.

GABA keeps nitric oxide in balance by regulating GSNOR to enhance disease resistance of harvested tomato against Botrytis cinerea

Gamma-aminobutyric acid (GABA), a widely distributed metabolite in prokaryotes and eukaryotes, has many functions for plants in stress responses. In this study, hypotonic treatment with 10 mmol L−1 GABA in cherry tomato induced resistance to Botrytis cinerea with markedly lower disease incidence and lesion diameter, led to endogenous nitric oxide (NO) tansient accumulation before inoculation the pathogen then decrease after inoculation, and enhanced the content of arginine (Arg) and glutamic acid (Glu). The resistance of fruit treated with a NO scavenger, carboxy-2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (cPTIO), was significantly reduced. Moreover, the enzyme activity and gene expression of S-nitrosoglutathione reductase (GSNOR) were enhanced following endogenous NO increased. The endogenous NO level was excessively high after treatment with a GSNOR scavenger, N6022, making the fruit more susceptible to pathogen. Similarly, after break down of SlGSNOR, fruit had much higher endogenous NO and lower disease resistance. However, overexpression of SlGSNOR exhibited opposite consequences. These results suggest that a suitable level of NO is beneficial for enhancing disease resistance, and GABA can help tomatoes maintain NO equilibrium by regulating GSNOR.

Nitric oxide (NO) involved in Cd tolerance in NHX1 transgenic duckweed during Cd stress

ABSTRACT Anthropogenic activities cause heavy metal pollution, such as cadmium (Cd). Na+/H+ antiporter (NHX1) transgenic duckweed showed Cd tolerance in our previous study, and the signal mechanism needs to be explored. As an important signal molecule, nitric oxide (NO) is involved in a number of functions under abiotic stress response. This study analyzed the levels of endogenous NO in wild-type (WT) duckweed and NHX1 duckweed under Cd treatment. The results showed that after 24 h Cd treatment, the endogenous NO level of WT duckweed decreased, which was significantly lower than that in NHX1 duckweed. Studies have proved that NHX1 influences pH. The level of NO in this study has been investigated at different pH. The NO level was the highest in the duckweed cultured with pH 5.3. Nitrate reductase gene expression was down-regulated and NO synthesis was decreased under Cd stress in WT duckweed. This study showed that NO level has been modified in NHX1 duckweed, which could be influcened by pH.

Nitric oxide-releasing nanomaterials: from basic research to potential biotechnological applications in agriculture.

Nitric oxide (NO) is a multifunctional gaseous signal that modulates the growth, development and stress tolerance of higher plants. NO donors have been used to boost plant endogenous NO levels and to activate NO-related responses, but this strategy is often hindered by the relative instability of donors. Alternatively, nanoscience offers a new, promising way to enhance NO delivery to plants, as NO-releasing nanomaterials (e.g. S-nitrosothiol-containing chitosan nanoparticles) have many beneficial physicochemical and biochemical properties compared to non-encapsulated NO donors. Nano NO donors are effective in increasing tissue NO levels and enhancing NO effects both in animal and human systems. The authors believe, and would like to emphasize, that new trends and technologies are essential for advancing plant NO research and nanotechnology may represent a breakthrough in traditional agriculture and environmental science. Herein, we aim to draw the attention of the scientific community to the potential of NO-releasing nanomaterials in both basic and applied plant research as alternatives to conventional NO donors, providing a brief overview of the current knowledge and identifying future research directions. We also express our opinion about the challenges for the application of nano NO donors, such as the environmental footprint and stakeholder's acceptance of these materials.

Sodium nitroprusside pretreatment alters responses of Chinese cabbage seedlings to subsequent challenging stresses

ABSTRACT Nitric oxide (NO) is a self-regulating gaseous molecule as well as an interacting partner with different reactive oxygen species (ROS). Endogenous NO increased, but hydrogen peroxide (H2O2) and superoxide radical anion () decreased in Chinese cabbage leaves treated with sodium nitroprusside (SNP) (0.5 mM). Antioxidant enzyme genes BrCat1, BrCat2, BrAPX, BrGR1, and BrGST1 expressions were transiently induced by the SNP (0.5 mM). Pretreated SNP (0.5 mM) enhanced tolerance to subsequent challenges by phytotoxic SNP (5 mM) and methyl viologen (MV) (50 μM), but accelerated cellular damage by H2O2 (4 M) shown by electrolyte leakage and lipid peroxidation. The SNP (0.5 mM) differentially modulated endogenous NO and ROS levels as well as antioxidant enzyme gene expressions by excess SNP, MV, and H2O2 stresses. These results suggest that NO as a signal molecule differentially interacts with challenging stresses in Chinese cabbage leaves, followed by differential cellular damage and antioxidant responses.

Endogenous nitric oxide contributes to chloride and sulphate salinity tolerance by modulation of ion transporter expression and reestablishment of redox balance in Brassica napus cultivars

Salinity is an adverse environmental stress for crop plants and the mechanism of salinity tolerance and its interaction with phytohormone like nitric oxide (NO) is still lacking, especially for Na2SO4 in B. napus. Therefore, in the present study, B. napus cultivars were grown under equimolar concentrations of NaCl/Na2SO4 and with their anions (KCl/K2SO4), to discriminate toxic responses of different types of salts on growth, oxidative stress, antioxidant defense, anion concentration and endogenous production of NO. Results showed that plant growth, photosynthetic rate and pigments productions were strongly inhibited under Na+ dominated salt treatments (NaCl/Na2SO4). As a result, production of oxidative stress (H2O2, O2.-, MDA, EL) related parameters were significantly induced under these treatments. The uptake of Na+ was high in B. napus cultivars irrespective of chloride/sulphate anions presence. However, Cl- and SO42- anions accumulation was only high in sensitive cultivars. The differential responses of B. napus cultivars against salinity treatments were associated with endogenous production of NO. The tolerant cultivar maintained higher level of NO, while sensitive cultivars experience a reduction in NO and inhibition of its biosynthesis enzymes, upon exposure to salinity treatments. To prove NO involvement, NO scavenger was applied on the leaves of B. napus cultivars, which significantly induced salt toxicity symptoms, oxidative stress and upregulated gene expression of ion transporters and uptake of Na+, Cl- and SO42-. Conversely, application of NO donor (sodium nitroprusside) reversed the salinity induce oxidative stress, ion accumulation and stimulated antioxidant defense in B. napus cultivars. Thus, the present study shows that endogenous NO level could act as an essential signaling molecule for triggering and activating the salinity adaptive response in rapeseed and Na+ toxicity plays a dominate role in growth inhibition, while the additive effect of chloride/sulphate anions may be cultivar dependent.

Repurposing of Hydroxyurea Against COVID-19: A Promising Immunomodulatory Role.

Cytokine release syndrome, a prominent mechanism of morbidity and mortality in patients with coronavirus disease 2019 (COVID-19), can cause multiple bodily reactions, including excessive release of proinflammatory mediators, with tumor necrosis factor-α (TNF-α) being the most prevalent cytokine combined with persistently elevated D-dimer levels that are indicative of potential thrombotic events, low levels of endogenous nitric oxide (NO) generation, and progressive decrease in hemoglobin production. In our argument, the conceptual repurposing of hydroxyurea (HU) for managing COVID-19 can provide a promising therapeutic option originating from a rich history of investigational antiviral activity. HU as a proposed supportive therapeutic agent for treating COVID-19 can exemplify a successful remedial choice through its anti-inflammatory activity along with an intrinsic propensity to control the circulatory levels of key cytokines including TNF-α. HU has the ability to undergo in vivo NO conversion acting as NO donor together with being a prominent inducer of fetal hemoglobin (HbF) production. The combination of the mentioned two properties allows HU to possess evident capability of protecting against thrombotic events by controlling D-dimer levels. The implication of our hypothetical argument sheds light on the curative potential of HU, which can be strategically harnessed against COVID-19.

Nitric oxide alleviates cadmium-impeded growth by limiting ROS accumulation in pea seedlings

Cadmium (Cd) causes oxidative stress, which leads to the oxidation of various biomolecules by the production of reactive oxygen species (ROS) to facilitate programmed cell death (PCD). The antioxidant defense system fails to detoxify ROS when it is produced in excess. Nitric oxide (NO), a gaseous free radical and a phytohormone, regulates various physiological processes of plants. Therefore, this work was undertaken to study the effects of the application of exogenous sodium nitroprusside (SNP, a NO donor) on growth parameters, oxidative stress, accumulation of secondary metabolites, and activities of antioxidant enzymes under Cd stress. Mild (50 µM) and severe (200 µM) Cd stress were applied to hydroponically grown pea (Pisum sativum L.) plants with or without 50 µM SNP. Severe Cd stress had a substantial impact on the plants. The effectiveness of NO in reducing Cd-induced negative effects on plant height, fresh weight, dry weight, protein content, nitrite content, nitrate reductase (NR) activity, catalase activity, and peroxidase activity were investigated. Seedling development, protein content, nitrite content, nitrate reductase (NR) activity, antioxidant defense systems disruption, overproduction of reactive oxygen species, and oxidative damage were observed. The antioxidant defense system (catalase and peroxidase activities) was activated by NO, which resulted in lower lipid peroxidation and lower hydrogen peroxide (H2O2) levels in Cd-exposed plants. SNP treatment boosted endogenous NO levels and NR activity in Cd-stressed plants while also enhanced proline levels to preserve osmotic equilibrium. The presence of total phenols and flavonoids increased after SNP treatment, indicating that SNP enhanced stress recovery and boosted plant development in Cd-stressed plants.

Spermine-Mediated Tolerance to Selenium Toxicity in Wheat (Triticum aestivum L.) Depends on Endogenous Nitric Oxide Synthesis

Excess selenium (Se) causes toxicity, and nitric oxide (NO)’s function in spermine (Spm)-induced tolerance to Se stress is unknown. Using wheat plants exposed to 1 mM sodium selenate—alone or in combination with either 1 mM Spm, 0.1 mM NO donor sodium nitroprusside (SNP) or 0.1 mM NO scavenger cPTIO—the potential beneficial effects of these compounds to palliate Se-induced stress were evaluated at physiological, biochemical and molecular levels. Se-treated plants accumulated Se in their roots (92%) and leaves (95%) more than control plants. Furthermore, Se diminished plant growth, photosynthetic traits and the relative water content and increased the levels of malondialdehyde, H2O2, osmolyte and endogenous NO. Exogenous Spm significantly decreased the levels of malondialdehyde by 28%, H2O2 by 37% and electrolyte leakage by 42%. Combined Spm/NO treatment reduced the Se content and triggered plant growth, photosynthetic traits, antioxidant enzymes and glyoxalase systems. Spm/NO also upregulated MTP1, MTPC3 and HSP70 and downregulated TaPCS1 and NRAMP1 (metal stress-related genes involved in selenium uptake, translocation and detoxification). However, the positive effects of Spm on Se-stressed plants were eliminated by the NO scavenger. Accordingly, data support the notion that Spm palliates selenium-induced oxidative stress since the induced NO elicits antioxidant defence upregulation but downregulates Se uptake and translocation. These findings pave the way for potential biotechnological approaches to supporting sustainable wheat crop production in selenium-contaminated areas.

Synergistic action of silicon nanoparticles and indole acetic acid in alleviation of chromium (CrVI) toxicity in Oryza sativa seedlings

The present study investigates ameliorative effect of silicon nanoparticles (SiNPs) and indole acetic acid (IAA) alone and in combination against hexavalent chromium (CrVI) toxicity in rice seedlings. The results of the study revealed protective effects of SiNPs and IAA against CrVI toxicity. The 100 μM of CrVI imposed toxic effects in rice seedlings at morphological, physiological and biochemical levels which coincided with increased level of intracellular CrVI and declined level of endogenous nitric oxide (NO). The CrVI enhanced levels of superoxide radicals (SOR) (59.51% and 50.1% in shoot and root, respectively) and H2O2 (19.5% and 23.69% in shoot and root, respectively). However, when SiNPs and IAA were applied to plants under CrVI stress, they enhanced tolerance and defence mechanisms as manifested in terms of increased biomass, endogenous NO, photosynthetic pigments, and antioxidants level. It was also noticed that CrVI arrested cell cycle at G2/M phase whereas growth was restored as compared to control when SiNPs and IAA were supplemented. Thus, the hypothesis that combined application of SiNPs and IAA will be effective in alleviating CrVI toxicity is validated from the results of this study. Moreover, in SiNPs and IAA-mediated mitigation of CrVI toxicity, endogenous NO has a positive role. The importance of the study will be that the combination of SiNPs and IAA can be utilized against heavy metal stress and even when supplied alone, they will enhance the crop productivity parameters with and without stress conditions.

The AtCRK5 Protein Kinase Is Required to Maintain the ROS NO Balance Affecting the PIN2-Mediated Root Gravitropic Response in Arabidopsis.

The Arabidopsis AtCRK5 protein kinase is involved in the establishment of the proper auxin gradient in many developmental processes. Among others, the Atcrk5-1 mutant was reported to exhibit a delayed gravitropic response via compromised PIN2-mediated auxin transport at the root tip. Here, we report that this phenotype correlates with lower superoxide anion (O2•−) and hydrogen peroxide (H2O2) levels but a higher nitric oxide (NO) content in the mutant root tips in comparison to the wild type (AtCol-0). The oxidative stress inducer paraquat (PQ) triggering formation of O2•− (and consequently, H2O2) was able to rescue the gravitropic response of Atcrk5-1 roots. The direct application of H2O2 had the same effect. Under gravistimulation, correct auxin distribution was restored (at least partially) by PQ or H2O2 treatment in the mutant root tips. In agreement, the redistribution of the PIN2 auxin efflux carrier was similar in the gravistimulated PQ-treated mutant and untreated wild type roots. It was also found that PQ-treatment decreased the endogenous NO level at the root tip to normal levels. Furthermore, the mutant phenotype could be reverted by direct manipulation of the endogenous NO level using an NO scavenger (cPTIO). The potential involvement of AtCRK5 protein kinase in the control of auxin-ROS-NO-PIN2-auxin regulatory loop is discussed.

Ascorbate and glutathione independently alleviate arsenate toxicity in brinjal but both require endogenous nitric oxide.

In this study, we have explored the possible role of ascorbic acid (ASC) and glutathione (GSH) in alleviating arsenate (AsV ) toxicity in brinjal roots. Moreover, we have also focused our attention on the possible involvement of endogenous nitric oxide (NO) in accomplishing this task. AsV treatment negatively impacts the length and fresh weight of roots and shoots as well as the dry weight and fitness of roots, and this was accompanied by greater As accumulation in roots and shoots of brinjal. AsV treatment also declined the endogenous NO level by inhibiting Nitric Oxide Synthase-like (NOS-like) activity. Furthermore, AsV stimulated oxidative stress markers, caused protein damage by their carbonylation due to downregulation in antioxidants [particularly ascorbate (AsA)-GSH cycle], leading to disturbed cellular redox status. This, collectively, led to root cell death in brinjal. However, the addition of either ASC or GSH rescued brinjal roots from the toxic effects of AsV in. Interestingly, lycorine (an inhibitor of ASC biosynthesis) further increased AsV toxicity, while ASC rescued its effects. Moreover, buthionine sulphoximine (BSO, an inhibitor of GSH biosynthesis) interestingly increased further AsV toxicity, while GSH rescued the plant from the As toxic effects. An interesting notion of this study was that GSH rescued the toxic effect of lycorine, while ASC rescued the toxic effect of BSO, though the AsV toxicity mediated by either ASC or GSH was always accompanied by high endogenous NO level and NOS-like activity. All together, these results suggest that ASC and GSH independently mitigate AsV toxicity in brinjal roots, but both might be dependent on endogenous NO for accomplishing the AsV toxicity alleviatory tasks.

A Double-blind, Placebo-controlled, Randomized, Longitudinal Study on the Effects of a Plant-based Dietary Supplement on Nitric Oxide and Mitochondrial Metabolic Activity

During the past two decades, metabolic dysfunction and concomitant reduction-oxidation reaction (redox) imbalances (i.e., oxidative stress) have been suggested to be associated with numerous age-related chronic diseases. One profound result of metabolic imbalances is endothelial dysfunction, a pathophysiological condition that increases risk of downstream chronic disease consequences. Healthy endothelial function has been positively associated with elevated levels of circulating nitric oxide (NO). Consequently, a natural, plant-based material that may safely increase endogenous NO levels, reduce redox imbalance, and promote improved metabolic response could be of significant interest and benefit. In this first study of its kind, we conducted a longitudinal, randomized, double-blind, placebo-controlled study of S7, a proprietary polyphenol-rich fruit, vegetable, and herb-based material previously reported to reduce reactive oxygen species (ROS) and to increase NO. Specifically, we measured changes in real-time cellular generation of ROS and changes in levels of bioavailable NO (measured as circulating NOHb) in 42 overweight or slightly obese individuals who were recruited into one of three groups: placebo, 25mg of S7, and 50mg of S7. Results suggest that after 90 days of once-daily supplementation, the 25mg and 50mg S7 groups exhibited diminished mitochondrial ROS generation (~54% and ~75%, respectively) compared to placebo, which exhibited a slight increase (>12%) (p = 0.049). Furthermore, circulating NOHb levels significantly increased in the 25mg and 50mg S7 groups (33.87% and 53.43%, respectively) compared to placebo (p < 0.001). Together, these results suggest that long-term daily supplementation of S7 may provide potential benefits related to healthy endothelial function and reduced mitochondrial dysfunction.

The prognostic implications of perioperative endogenous hydrogen sulfide and nitric oxide levels in children with congenital heart disease complicated by pulmonary arterial hypertension.

The goal of this study was to measure perioperative changes in endogenous hydrogen sulfide (H2S) and nitric oxide (NO) levels in children with congenital heart disease (CHD) complicated by pulmonary arterial hypertension (PAH), with the goal of better monitoring these children and evaluating their prognosis. For this study, we enrolled 48 normal control cases, 48 preoperative CHD cases including 16 without PAH, 16 with mild PAH, and 16 with moderate-to-severe PAH. We additionally enrolled a cohort of 32 other children with PAH-CHD that had undergone CHD correction prior to transfer to an intensive care unit (ICU). These children were further subdivided based on whether or not PAH was still present after operation (n = 16 per group). Spectrophotometry was used to assess endogenous H2S and NO levels at 24 and 48h postoperatively in each group. Correlations between postoperative endogenous H2S and NO levels at these two time points, as well as duration of mechanical ventilation, ICU length of stay, duration of hospitalization, and vasoactive drug score values at 24 and 48h postoperation were assessed. Endogenous H2S and NO values differed significantly between the control and preoperative CHD groups (P < 0.05). These values also differed significantly among the three different preoperative CHD subgroups and were negatively correlated with pulmonary arterial pressure (P < 0.05). Spearman rank correlation analyses indicated that endogenous H2S levels at 24 and 48h postoperation were negatively correlated with the duration of mechanical ventilation, ICU length of stay, and maximum vasoactive drug score values at both 24 and 48h postoperation. We similarly identified a negative correlation between NO concentrations at 24 and 48h postoperation and maximum vasoactive drug score at these same time points (P < 0.05).Conclusions: Endogenous H2S and NO levels are closely associated with CHD-PAH incidence, and there is a correlation between endogenous H2S levels and the postoperative prognosis of CHD in children. Higher H2S concentrations seem to correspond to better patient prognosis, and as such these values can be used as a prognostic index at an early time point. These values can additionally guide treatment efforts and improve outcomes among children with CHD-PAH. What is Known: • Hydrogen sulfide and nitric oxide are both vasodilating factors. • Hydrogen sulfide and nitric oxide can regulate pulmonary vascular remodeling, which is closely related to the occurrence and prognosis of pulmonary arterial hypertension. What is New: • This study was designed to explore the relationship between short-term prognostic indexes and hydrogen sulfide and nitric oxide levels, in an effort to provide a frame of reference for the postoperative monitoring and treatment of children with congenital heart disease complicated by pulmonary arterial hypertension.

Bioinspired Design of Reversible Fluorescent Probes for Tracking Nitric Oxide Dynamics in Live Cells

Bioinspired Design of Reversible Fluorescent Probes for Tracking Nitric Oxide Dynamics in Live Cells

Trehalose triggers hydrogen peroxide and nitric oxide to participate in melon seedlings oxidative stress tolerance under cold stress

Cold stress is an important environmental factor restricting the cultivation of melons in winter and spring. Exogenous trehalose (Tre) can improve the stress tolerance of crops. However, the mechanistic role of Tre in regulating crop cold tolerance is not completely clear and whether hydrogen peroxide (H2O2) and nitric oxide (NO) act as signalling molecules in Tre regulation melon cold tolerance remains unknown. Thus, this study was conducted to analyse the cold tolerance of cold-tolerant (IVF571) and cold-sensitive (IVF004) melon varieties and their H2O2 and NO levels. Then, the roles of exogenous Tre in regulating the cold tolerance of melons and the interaction of H2O2 and NO in Tre-regulated cold tolerance were investigated. Results showed that the damage to membrane lipid peroxidation in IVF571 plants was significantly slighter than that in IVF004 plants, and the levels of H2O2 and NO in IVF571 plants were significantly higher than those in IVF004 plants under cold stress. Exogenous Tre was more effective than sucrose and glucose in significantly increasing the maximal quantum yield of PSII photochemistry, reducing the relative electrical conductivity in melon leaves under cold stress by increasing the superoxide dismutase (SOD) activity under normal conditions and enhancing SOD, glutathione reductase and ascorbate peroxidase activities and GSH/GSSG ratio under cold stress. Exogenous Tre could induce the increase in H2O2 and NO levels. The removal of endogenous H2O2 with dimethylthiourea weakened the role of exogenous Tre, whereas eliminating NO with 2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide almost abolished the effects of exogenous Tre and H2O2. In summary, the higher cold tolerance of IVF571 seedlings than that of IVF004 seedlings might be related to the increase in H2O2 and NO levels triggered by cold stress. Tre might have a unique effect on the regulation of cold-induced oxidative stress in melon. Tre could elevate endogenous H2O2 and NO levels, which stimulated the stress response system of melon. Consequently, when melon plants were exposed to cold stress, antioxidant enzyme activities improved, and the damage to membrane lipid peroxidation was reduced. In this process, H2O2 and NO participated in the roles of Tre, and NO might be located downstream of H2O2.

Nitric Oxide Overproduction by cue1 Mutants Differs on Developmental Stages and Growth Conditions.

The cue1 nitric oxide (NO) overproducer mutants are impaired in a plastid phosphoenolpyruvate/phosphate translocator, mainly expressed in Arabidopsis thaliana roots. cue1 mutants present an increased content of arginine, a precursor of NO in oxidative synthesis processes. However, the pathways of plant NO biosynthesis and signaling have not yet been fully characterized, and the role of CUE1 in these processes is not clear. Here, in an attempt to advance our knowledge regarding NO homeostasis, we performed a deep characterization of the NO production of four different cue1 alleles (cue1-1, cue1-5, cue1-6 and nox1) during seed germination, primary root elongation, and salt stress resistance. Furthermore, we analyzed the production of NO in different carbon sources to improve our understanding of the interplay between carbon metabolism and NO homeostasis. After in vivo NO imaging and spectrofluorometric quantification of the endogenous NO levels of cue1 mutants, we demonstrate that CUE1 does not directly contribute to the rapid NO synthesis during seed imbibition. Although cue1 mutants do not overproduce NO during germination and early plant development, they are able to accumulate NO after the seedling is completely established. Thus, CUE1 regulates NO homeostasis during post-germinative growth to modulate root development in response to carbon metabolism, as different sugars modify root elongation and meristem organization in cue1 mutants. Therefore, cue1 mutants are a useful tool to study the physiological effects of NO in post-germinative growth.

Nitric Oxide (NO) and NO Synthases (NOS)-Based Targeted Therapy for Colon Cancer.

Colorectal cancer (CRC) is one of the most lethal malignancies worldwide and CRC therapy remains unsatisfactory. In recent decades, nitric oxide (NO)—a free-radical gas—plus its endogenous producer NO synthases (NOS), have attracted considerable attention. NO exerts dual effects (pro- and anti-tumor) in cancers. Endogenous levels of NO promote colon neoplasms, whereas exogenously sustained doses lead to cytotoxic functions. Importantly, NO has been implicated as an essential mediator in many signaling pathways in CRC, such as the Wnt/β-catenin and extracellular-signal-regulated kinase (ERK) pathways, which are closely associated with cancer initiation, metastasis, inflammation, and chemo-/radio-resistance. Therefore, NO/NOS have been proposed as promising targets in the regulation of CRC carcinogenesis. Clinically relevant NO-donating agents have been developed for CRC therapy to deliver a high level of NO to tumor sites. Notably, inducible NOS (iNOS) is ubiquitously over-expressed in inflammatory-associated colon cancer. The development of iNOS inhibitors contributes to targeted therapies for CRC with clinical benefits. In this review, we summarize the multifaceted mechanisms of NO-mediated networks in several hallmarks of CRC. We review the clinical manifestation and limitations of NO donors and NOS inhibitors in clinical trials. We also discuss the possible directions of NO/NOS therapies in the immediate future.