Protein Nitration Research Articles

Revealing the metabolic potential and environmental adaptation of nematophagous fungus, Purpureocillium lilacinum, derived from hadal sediment

The extreme environment shapes fungi in deep-sea sediments with novel metabolic capabilities. The ubiquity of fungi in deep-sea habitats supports their significant roles in these ecosystems. However, there is limited research on the metabolic activities and adaptive mechanisms of filamentous fungi in deep-sea ecosystems. In this study, we investigated the biological activities, including antibacterial, antitumor and nematicidal activity of Purpureocillium lilacinum FDZ8Y1, isolated from sediments of the Mariana Trench. A key feature of P. lilacinum FDZ8Y1 was its tolerance to high hydrostatic pressure (HHP), up to 110 MPa. We showed that HHP affected its vegetative growth, development, and production of secondary metabolites, indicating the potential for discovering novel natural products from hadal fungi. Whole-genome sequencing of P. lilacinum FDZ8Y1 revealed the metabolic potential of this piezotolerant fungus in carbon (carbohydrate metabolism), nitrogen (assimilatory nitrate reduction and protein degradation) and sulfur cycling processes (assimilatory sulfate reduction). Transcriptomic analysis under elevated HHP showed that P. lilacinum FDZ8Y1 may activate several metabolic pathways and stress proteins to cope with HHP, including fatty acid metabolism, the antioxidant defense system, the biosynthetic pathway for secondary metabolites, extracellular enzymes and membrane transporters. This study provides valuable insights into the metabolic potential and adaptation mechanisms of hadal fungi to the challenging conditions of the hadal environment.

Resveratrol relieves myocardial ischemia–reperfusion injury through inhibiting AKT nitration modification

ABSTRACT Objective The aim of this study was to clarify whether Protein kinase B (PKB)/AKT is nitrated in myocardial ischemia and reperfusion injury (MIRI) resveratrol (RSV)’s protective effect during this process. Methods We blocked blood flow of the left coronary artery (LAD) of mice and used H9c2 cells under an oxygen-glucose deprivation (OGD) environment as animal and cell models of MIRI. N-methyl-D-aspartic acid receptor (NMDAR) inhibitor MK801, neuronal nitric oxide synthase (nNOS) inhibitor 7-NI and RSV were used as interventions. Nitration of proteins, infarction area, cardiomyocyte apoptosis and AKT nitration sites were detected during this study. Results During in-vivo study, AKT nitration was induced through the NMDAR/nNOS/peroxynitrite (ONOO–) pathway, leading to decreased phosphorylation of AKT and increased cardiomyocyte apoptosis. AKT nitration was decreased and phosphorylation was elevated when administrated with RSV, MK801 and 7-NI. In in-vitro study, AKT nitration and TUNEL positive cells was elevated when administrated with NO donor H9c2 cells after OGD/R, when administrated with RSV, MK801 and 7-NI, AKT nitration and apoptosis was deceased in H9c2 cells. Mass spectrometry revealed that nitration sites of AKT included 14 Tyrosine residues. Discussion RSV could inhibit AKT nitration and elevated phosphorylation through suppressing NMDAR/nNOS/ONOO– pathway and further reduce the apoptosis of cardiomyocytes in of myocardial I/R.

The Interplay of Nitric Oxide and Nitrosative Modifications in Maize: Implications for Aphid Herbivory and Drought Stress.

Nitric oxide (NO) and other reactive nitrogen species (RNS) are considered to be signaling molecules in higher plants involved in the regulation of growth and development processes. However, the molecular mechanisms of their formation, removal, and participation in plant responses to adverse environmental stimuli remain largely unclear. Therefore, the aim of this study was to assess the influence of selected single stresses and combined stresses (i.e., Rhopalosiphum padi L. aphid infestation, drought, aphid infestation, and drought) and post-stress recovery on the contents of NO and peroxynitrite anion (ONOO-), as well as the levels of mRNA and protein nitration (i.e., the 8-nitroguanine and protein 3-nitrotyrosine amounts, respectively), in maize seedlings (Zea mays L.). Moreover, the expression patterns of the two tested genes (nos-ip, encoding nitric oxide synthase-interacting protein, and nr1, encoding nitrate reductase 1) involved in NO metabolism in maize plants were quantified. We identified significant intervarietal, time-course, and stress-dependent differences in the levels of the quantified parameters. Under the investigated stress conditions, the aphid-resistant Waza cv. seedlings were characterized by a higher and earlier NO accumulation and mRNA nitration level and an increased expression of the two target genes (nos-ip and nr1), compared to the aphid-susceptible Złota Karłowa cv. seedlings. Conversely, the Złota Karłowa plants responded with a greater elevation in the content of ONOO- and protein 3-nitrotyrosine than the Waza cv. plants The multifaceted role of NO and its derivatives in maize plants challenged by single and combined stresses, as well as during post-stress recovery, is discussed.

Neudesin, a secretory protein, attenuates activation of lipopolysaccharide-stimulated macrophages by suppressing the Jak/Stat1/iNOS pathway

AimsNeudesin, a heme-binding protein previously identified for its neurotrophic activity, has been implicated in various physiological and pathological processes, including immune regulation. However, its role in inflammatory macrophages remains unclear. Herein, we investigated the function of neudesin in the regulation of inflammatory macrophages. Main methodsIn vitro experiments were performed in bone marrow-derived macrophages (BMDMs). In vivo experiments were conducted on neudesin knockout mice with a murine endotoxic shock model. Key findingsWe observed that neudesin deficiency led to elevated expression of Nos2/iNOS and increased nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated BMDMs. Further, we found that neudesin, via the ERK/MAPK signaling pathway, promotes the proteasome-mediated degradation of Stat1, resulting in suppression of NO production. Furthermore, neudesin-deficient mice exhibited higher mortality rates following LPS administration, accompanied by increased Nos2/iNOS expression and nitrated proteins in the heart, compared to that in wildtype mice. Treatment with an iNOS inhibitor drastically improved the survival rate of neudesin-deficient mice, highlighting the significance of neudesin-mediated iNOS signaling in modulating immune responses and preventing excessive inflammation. SignificanceOur findings suggest that neudesin acts as an anti-inflammatory cytokine, suppressing NO production in inflammatory macrophages, underscoring its potential as a therapeutic target for immune-related disorders.

Nitric oxide synthase system in the brain development of neonatal hypothyroid rats

Thyroid hormones play an important morphogenetic role during the fetal and neonatal periods and regulate numerous metabolic processes. In the central nervous system, they control myelination and overall brain development, regional gene expression, and regulation of oxygen consumption. Their deficiency in the fetal and neonatal periods causes severe mental retardation, due to lack of thyroid function, or to iodine deficiency. At the same time, nitric oxide is an atypical neurotransmitter that also has special relevance in neuronal development and plasticity and functions as a vasodilator, regulating cerebral blood flow. Although under physiological conditions it functions as a neuroprotector, in excess it can be neurotoxic. We have studied, by immunocytochemical and Western blot techniques, the evolution of the expression of neuronal and inducible isoforms of the enzyme nitric oxide synthase, and of nitrotyrosine as a marker of protein nitration produced by the presence of nitric oxide, during the early stages of postnatal brain development. We induced hypothyroidism by administering mercaptomethylimidazole to pregnant mothers, from the seventh day of gestation until the sacrifice of the offspring. The results show a delay in the evolution of the expression of the two isoforms of the enzyme nitric oxide synthase in hypothyroid animals, followed by an anomalous overexpression in later stages. Finally, the expression of nitrotyrosine follows an evolution that is synchronized with that shown by both isoenzymes in control and hypothyroid animals.

Ultraviolet irradiation enhances the nitration of allergens

Ultraviolet (UV) light is widely used for disinfection in indoor environments. Some wavelengths of UV light can produce high concentration of O3. UV irradiation combined with O3 may have great potential for nitration of allergens in the presence of NO2 in the air. In this study, the effects of UV irradiation on the nitration of three major indoor allergens including group Ⅰ allergens of house dust mite (Der p 1 and Der f 1) and group Ⅰ allergen of dog (Can f 1) in the presence of NO2 and O3 were investigated by analysis of the protein quantity, tyrosine, peptides, and nitration degree. The results showed that UV irradiation induced a significant increase in the quantity of 3-nitrotyrosine in the allergens from 0.4 ± 0.4 ng to 4.0 ± 0.8 ng. After 12 h of UV-O3 co-exposure, the total nitration degrees of the three allergens ranged from 0.1% to 0.5%, which were significantly higher than those after only O3 exposure (p < 0.05). The analysis of peptides revealed that the nitration of tyrosine was site-specific. The tyrosine Y231, which was adjacent to aspartic acid, posed the highest nitration degree of 41.1 ± 24.0% in Der p 1. The nitration degree of tyrosine Y162 was the highest (1.7 ± 0.1%) in Der f 1. Overall, this study demonstrated that UV irradiation enhanced the O3-related nitration of allergens in the air, which provides an experimental basis for the impact of daily disinfection behavior on allergens.

Absence of mitochondrial CX9C-CX10C protein Cox12 generates oxidative and nitrosative stress in Saccharomyces cerevisiae: Implication on cellular redox homeostasis

Mitochondrial intermembrane space (IMS) harbors a series of small, evolutionarily conserved redox-active cysteine-rich proteins. These proteins are essential for the functioning of cytochrome c oxidase, but their role in maintaining cellular redox processes is unknown. Here, we find out that in the absence of two such cysteine-rich Cx9C-Cx10C proteins, cytochrome c oxidase subunit 12 (Cox12) or cytochrome c oxidase assembly factor 6 (Coa6), Saccharomyces cerevisiae cells become sensitive under the oxidative and nitrosative stress. Interestingly, knockout of COX12 generates a significant amount of endogenous reactive oxygen species (ROS) and reactive nitrogen species (RNS) as evidenced by FACS analysis. Moreover, cellular redox status, redox-active enzymes glutathione reductase, catalase, S-nitroso glutathione reductase, and protein nitration were significantly affected in Cox12 null cells. Further, we found that an overexpression of COX12 partially protects mitochondrial respiratory subunit Sdh2 under oxidative and nitrosative stress. Taken together, we provide proof of evidence that cysteine-rich proteins in the IMS dynamically control the cellular redox milieu and actively prevent reactive nitrogen and oxygen species generation.

Nuclear Localization of Human SOD1 in Motor Neurons in Mouse Model and Patient Amyotrophic Lateral Sclerosis: Possible Links to Cholinergic Phenotype, NADPH Oxidase, Oxidative Stress, and DNA Damage.

Amyotrophic lateral sclerosis (ALS) is a fatal disease that causes degeneration of motor neurons (MNs) and paralysis. ALS can be caused by mutations in the gene that encodes copper/zinc superoxide dismutase (SOD1). SOD1 is known mostly as a cytosolic antioxidant protein, but SOD1 is also in the nucleus of non-transgenic (tg) and human SOD1 (hSOD1) tg mouse MNs. SOD1's nuclear presence in different cell types and subnuclear compartmentations are unknown, as are the nuclear functions of SOD1. We examined hSOD1 nuclear localization and DNA damage in tg mice expressing mutated and wildtype variants of hSOD1 (hSOD1-G93A and hSOD1-wildtype). We also studied ALS patient-derived induced pluripotent stem (iPS) cells to determine the nuclear presence of SOD1 in undifferentiated and differentiated MNs. In hSOD1-G93A and hSOD1-wildtype tg mice, choline acetyltransferase (ChAT)-positive MNs had nuclear hSOD1, but while hSOD1-wildtype mouse MNs also had nuclear ChAT, hSOD1-G93A mouse MNs showed symptom-related loss of nuclear ChAT. The interneurons had preserved parvalbumin nuclear positivity in hSOD1-G93A mice. hSOD1-G93A was seen less commonly in spinal cord astrocytes and, notably, oligodendrocytes, but as the disease emerged, the oligodendrocytes had increased mutant hSOD1 nuclear presence. Brain and spinal cord subcellular fractionation identified mutant hSOD1 in soluble nuclear extracts of the brain and spinal cord, but mutant hSOD1 was concentrated in the chromatin nuclear extract only in the spinal cord. Nuclear extracts from mutant hSOD1 tg mouse spinal cords had altered protein nitration, footprinting peroxynitrite presence, and the intact nuclear extracts had strongly increased superoxide production as well as the active NADPH oxidase marker, p47phox. The comet assay showed that MNs from hSOD1-G93A mice progressively (6-14 weeks of age) accumulated DNA single-strand breaks. Ablation of the NCF1 gene, encoding p47phox, and pharmacological inhibition of NADPH oxidase with systemic treatment of apocynin (10 mg/kg, ip) extended the mean lifespan of hSOD1-G93A mice by about 25% and mitigated genomic DNA damage progression. In human postmortem CNS, SOD1 was found in the nucleus of neurons and glia; nuclear SOD1 was increased in degenerating neurons in ALS cases and formed inclusions. Human iPS cells had nuclear SOD1 during directed differentiation to MNs, but mutant SOD1-expressing cells failed to establish wildtype MN nuclear SOD1 levels. We conclude that SOD1 has a prominent nuclear presence in the central nervous system, perhaps adopting aberrant contexts to participate in ALS pathobiology.

Protective Role of Polyethylene Glycol Towards the Damaging Effects of Cadmium.

This study aimed to evaluate the role of drought-induced changes in the effects of cadmium (Cd) in plants. Cd is the most hazardous and important environmental pollutant. Water deficit is the most common environmental stress encountered by plants and affects most of the plant functions. The present study assessed the effect of Cd and water deficit on Capsicum frutescens seedlings in single and combined treatments. The seedlings of Capsicum were grown in a hydroponic solution and treated with Cd. The seedlings were subjected to water deficit with the help of polyethylene glycol (PEG). The other set of seedlings was treated with combined Cd + PEG. In the absence of PEG, maximum Cd accumulation was observed. The root and shoot growth of the seedlings were affected under all treatments with maximum inhibition in Cd. Pigment, protein and sugar contents and nitrate reductase activity decreased significantly in all treatments, while proline content increased. Induction of oxidative damage occurred through the formation of free radicals which caused alteration in electrolyte leakage, lipid peroxidation and activities of antioxidant enzymes, viz. superoxide dismutase, catalase, ascorbate peroxidase, guaiacol peroxidase and non-enzymatic non-protein thiol content and ascorbic acid in the stressed seedlings. Water deficit buttressed the toxic effect of Cd on chilli seedlings.

Selective nitration of Hsp90 acts as a metabolic switch promoting tumor cell proliferation

Tumors develop in an oxidative environment characterized by peroxynitrite production and downstream protein tyrosine (Y) nitration. We showed that tyrosine nitration supports schwannoma cell proliferation and regulates cell metabolism in the inheritable tumor disorder NF2-related Schwannomatosis (NF2-SWN). Here, we identified the chaperone Heat shock protein 90 (Hsp90) as the first nitrated protein that acts as a metabolic switch to promote schwannoma cell proliferation. Doubling the endogenous levels of nitrated Hsp90 in schwannoma cells or supplementing nitrated Hsp90 into normal Schwann cells increased their proliferation. Metabolically, nitration on either Y33 or Y56 conferred Hsp90 distinct functions; nitration at Y33 (Hsp90NY33) down-regulated mitochondrial oxidative phosphorylation, while nitration at Y56 (Hsp90NY56) increased glycolysis by activating the purinergic receptor P2X7 in both schwannoma and normal Schwann cells. Hsp90NY33 and Hsp90NY56 showed differential subcellular and spatial distribution corresponding with their metabolic and proliferative functions in schwannoma three-dimensional cell culture models. Collectively, these results underscore the role of tyrosine nitration as a post-translational modification regulating critical cellular processes. Nitrated proteins, particularly nitrated Hsp90, emerge as a novel category of tumor-directed therapeutic targets.

Protein nitration in the artery wall: A contributor to cardiovascular disease?

Nitration is a well-established post-translational modification of selected free amino acids, as well as proteins, lipids and nucleic acids. Considerable evidence is now available for the formation of long-lived species containing an added –NO2 function on the aromatic rings of tyrosine (Tyr) and tryptophan (Trp) residues (both free and on proteins), to purine nucleobases (and particularly guanine), and to unsaturated lipids within biological systems. Multiple potential mechanisms that give rise to these nitrated species have been identified including reactions of the potent oxidant and nitrating species peroxynitrous acid/peroxynitrite (ONOOH/ONOO−) and via oxidative reactions of heme proteins/enzymes (e.g. peroxidases) with the biologically-relevant anion nitrite (NO2−). •NO2 is likely to be a key intermediate, though involvement of HNO2, NO2+ and NO2Cl has also been proposed. The resulting nitrated products have been widely employed as qualitative or quantitative biomarkers of nitration events in vitro and in vivo. Increasing evidence suggests that at least some of these products are not benign species, with evidence for pro-inflammatory actions. In this article the mechanisms and role of nitration, and particularly that on proteins within the artery wall, in cardiovascular disease is discussed, together with emerging data suggesting that low levels of nitration occur within biological systems in the absence of added oxidants. Both stimulated and endogenous nitration may play a role in modulating cell signaling, alter the structure and function of both cellular- and extracellular proteins, and contribute to various inflammatory pathologies, including atherosclerosis.

Identification of nitrated proteins in human thrombi from ischemic cerebrovascular events

Identification of nitrated proteins in human thrombi from ischemic cerebrovascular events

Daily white tea intake reprograms hepatic metabolism and improves the enzymatic antioxidant defence system of rats with prediabetes

BackgroundPrediabetes (PrDM) poses a significant risk for the development of Diabetes Mellitus (DM). Preventing the transition to type 2 DM is of utmost importance, and identifying novel dietary agents with both antioxidant and antidiabetic properties is crucial. This study aims to assess the potential of regular white tea (WTEA) consumption in alleviating the detrimental effects of PrDM on hepatic metabolism and redox state. MethodsTo achieve this, we divided 18 male Wistar rats into three groups: a control group and two prediabetes (PrDM) groups. In one of the PrDM groups, water consumption was replaced with white tea (WTEA). After a two-month period, we evaluated the hepatic metabolic profile using 1H NMR. Additionally, we measured total antioxidant potential, the activities of antioxidant enzymes, and various oxidative parameters, including protein nitration and carbonylation, lipid peroxidation, and levels of H2A.X and phosphorylated H2A.X. ResultsPrDM induced a decline in hepatic catabolic metabolism and the activities of key antioxidant enzymes, including superoxide dismutase, glutathione reductase, catalase, and levels of phosphorylated H2A.X. However, when PrDM rats consumed WTEA, a remarkable restoration occurred. Specifically, WTEA intake reinstated glutathione reductase and catalase activities and elevated superoxide dismutase activity in the liver compared to normoglycemic conditions. Moreover, enhancements were noted in overall antioxidant capacity and a reduction in lipid peroxidation in the rat liver. ConclusionPrDM significantly impacts liver metabolism and antioxidant defenses, but the consumption of WTEA, a plant-based functional beverage, exhibits potent hepatoprotective capabilities against PrDM-induced oxidative stress.

The bacterial metabolite, lithocholic acid, has antineoplastic effects in pancreatic adenocarcinoma

Lithocholic acid (LCA) is a secondary bile acid. LCA enters the circulation after bacterial synthesis in the gastrointestinal tract, reaches distantly located cancer cells, and influences their behavior. LCA was considered carcinogenic, but recent studies demonstrated that LCA has antitumor effects. We assessed the possible role of LCA in pancreatic adenocarcinoma. At the serum reference concentration, LCA induced a multi-pronged antineoplastic program in pancreatic adenocarcinoma cells. LCA inhibited cancer cell proliferation and induced mesenchymal-to-epithelial (MET) transition that reduced cell invasion capacity. LCA induced oxidative/nitrosative stress by decreasing the expression of nuclear factor, erythroid 2-like 2 (NRF2) and inducing inducible nitric oxide synthase (iNOS). The oxidative/nitrosative stress increased protein nitration and lipid peroxidation. Suppression of oxidative stress by glutathione (GSH) or pegylated catalase (pegCAT) blunted LCA-induced MET. Antioxidant genes were overexpressed in pancreatic adenocarcinoma and decreased antioxidant levels correlated with better survival of pancreatic adenocarcinoma patients. Furthermore, LCA treatment decreased the proportions of cancer stem cells. Finally, LCA induced total and ATP-linked mitochondrial oxidation and fatty acid oxidation. LCA exerted effects through the farnesoid X receptor (FXR), vitamin D receptor (VDR), and constitutive androstane receptor (CAR). LCA did not interfere with cytostatic agents used in the chemotherapy of pancreatic adenocarcinoma. Taken together, LCA is a non-toxic compound and has antineoplastic effects in pancreatic adenocarcinoma.

Protein Oxidation in Aging and Alzheimer's Disease Brain.

Proteins are essential molecules that play crucial roles in maintaining cellular homeostasis and carrying out biological functions such as catalyzing biochemical reactions, structural proteins, immune response, etc. However, proteins also are highly susceptible to damage by reactive oxygen species (ROS) and reactive nitrogen species (RNS). In this review, we summarize the role of protein oxidation in normal aging and Alzheimer's disease (AD). The major emphasis of this review article is on the carbonylation and nitration of proteins in AD and mild cognitive impairment (MCI). The oxidatively modified proteins showed a strong correlation with the reported changes in brain structure, carbohydrate metabolism, synaptic transmission, cellular energetics, etc., of both MCI and AD brains compared to the controls. Some proteins were found to be common targets of oxidation and were observed during the early stages of AD, suggesting that those changes might be critical in the onset of symptoms and/or formation of the pathological hallmarks of AD. Further studies are required to fully elucidate the role of protein oxidation and nitration in the progression and pathogenesis of AD.

Identification of nitrated proteins in human thrombi from ischemic cerebrovascular events

Identification of nitrated proteins in human thrombi from ischemic cerebrovascular events

Long-term fertilization and manuring effects on the nexus between sulphur distribution and SOC in an Inceptisol over five decades under a finger millet–maize cropping system

Our investigation revealed that alterations in sulphur (S) pools are predominantly governed by soil organic carbon (SOC), soil nitrogen (N), microbial biomass, and soil enzyme activities in sandy clay loam (Vertic Ustropept) soil. We employed ten sets of nutrient management techniques, ranging from suboptimal (50% RDF) to super-optimal doses (150% RDF), including NPK + Zn, NP, N alone, S-free NPK fertilizers, NPK + FYM, and control treatments, to examine the interrelation of S with SOC characteristics. Fourier-transform infrared (FT-IR) spectroscopy was utilized to analyze the functional groups present in SOC characterization across four treatments: 100% NPK, 150% NPK, NPK + FYM, and absolute control plots. Principal component analysis (PCA) was then applied to assess 29 minimal datasets, aiming to pinpoint specific soil characteristics influencing S transformation. In an Inceptisol, the application of fertilizers (100% RDF) in conjunction with 10 t ha−1 of FYM resulted in an increase of S pools from the surface to the subsurface stratum (OS > HSS > SO42−–S > WSS), along with an increase in soil N and SOC. FT-IR spectroscopy identified cellulose and thiocyanate functional groups in all four plots, with a pronounced presence of carbohydrate—protein polyphenol, sulfoxide (S=O), and nitrate groups specifically observed in the INM plot. The PCA findings indicated that the primary factors influencing soil quality and crop productivity (r2 of 0.69) are SOC, SMBC, SMBN, SMBS, and the enzyme activity of URE, DHA, and AS. According to the study, the combined application of fertilizer and FYM (10 t ha−1) together exert a positive impact on sulphur transformation, SOC accumulation, and maize yield in sandy clay loam soil.

Quantitative profiling of cochlear synaptosomal proteins in cisplatin-induced synaptic dysfunction

The disruption of ribbon synapses in the cochlea impairs the transmission of auditory signals from the cochlear sensory receptor cells to the auditory cortex. Although cisplatin-induced loss of ribbon synapses is well-documented, and studies have reported nitration of cochlear proteins after cisplatin treatment, yet the underlying mechanism of cochlear synaptopathy is not fully understood. This study tests the hypothesis that cisplatin treatment alters the abundance of cochlear synaptosomal proteins, and selective targeting of nitrative stress prevents the associated synaptic dysfunction. Auditory brainstem responses of mice treated with cisplatin showed a reduction in amplitude and an increase in latency of wave I, indicating cisplatin-induced synaptic dysfunction. The mass spectrometry analysis of cochlear synaptosomal proteins identified 102 proteins that decreased in abundance and 249 that increased in abundance after cisplatin treatment. Pathway analysis suggested that the dysregulated proteins were involved in calcium binding, calcium ion regulation, synapses, and endocytosis pathways. Inhibition of nitrative stress by co-treatment with MnTBAP, a peroxynitrite scavenger, attenuated cisplatin-induced changes in the abundance of 27 proteins. Furthermore, MnTBAP co-treatment prevented the cisplatin-induced decrease in the amplitude and increase in the latency of wave I. Together, these findings suggest a potential role of oxidative/nitrative stress in cisplatin-induced cochlear synaptic dysfunction.

Potassium humate supplementation improves photosynthesis and agronomic and yield traits of foxtail millet

Foxtail millet is a highly nutritious crop, which is widely cultivated in arid and semi-arid areas worldwide. Humic acid (HA), as a common plant growth regulator, is used as an organic fertilizer and feed additive in agricultural production. However, the impact of potassium humate KH on the photosynthetic rate and yield of foxtail millet has not yet been studied. We explored the effects of KH application on the morphology, photosynthetic ability, carbon and nitrogen metabolism, and yield of foxtail millet. A field experiment was performed using six concentrations of KH (0, 20, 40, 80, 160, and 320 kg ha−1) supplied foliarly at the booting stage in Zhangza 10 cultivar (a widely grown high-yield variety). The results showed that KH treatment increased growth, chlorophyll content (SPAD), photosynthetic rate (Pn), transpiration rate (Tr), and stomatal conductance (Gs). In addition, soluble protein content, sugar content, and nitrate reductase activity increased in KH-treated plants. With increased KH concentration, the effects became more evident and the peak values of each factor were achieved at 80 kg ha−1. Photosynthetic rate showed significant correlation with SPAD, Tr, Gs, and soluble protein content, but was negatively correlated with intercellular CO2 concentration. Compared to that of the control, the yield of foxtail millet under the T2, T3, T4, and T5 (40, 80, 160, and 320 kg ha−1 of KH) treatments significantly increased by 6.0%, 12.7%, 10.5%, and 8.6%, respectively. Yield exhibited a significant positive correlation with Tr, Pn, and Gs. Overall, KH enhances photosynthetic rate and yield of foxtail millet, therefore it may be conducive to stable millet production. These findings may provide a theoretical basis for the green and efficient production of millet fields.

Arginine ingestion inhibits phagocyte invasion in eccentrically contracted rat fast-twitch muscle.

Eccentric contraction (ECC) has been shown to induce leukocyte invasion into skeletal muscle, resulting in muscle inflammation. This study aimed to investigate whether prior ingestion of L-arginine (ARG), a nitric oxide precursor, inhibits ECC-induced macrophage invasion. Male Wistar rats received ARG in water for 7days, beginning 3days prior to ECC. ECCs were induced in the anterior crural muscles for 200 cycles. Three days later, the tibialis anterior and extensor digitorum longus muscles were excised for biochemical analysis and force measurement, respectively. ARG ingestion increased nitrite and nitrate levels in plasma and muscle, inhibiting force depression and reducing CD68 content in muscles subjected to ECC. ARG ingestion also ameliorated an ECC-induced increase in protein nitration, although neither ARG ingestion nor ECC induction affected protein carbonyl levels. The present results suggest that ingestion of ARG or ARG-rich foods may alleviate inflammation by attenuating phagocyte invasion in eccentrically contracted skeletal muscles.