Carbonyl Species Research Articles

Reactivity of low-valent nickel carbonyl species supported by acridane based PNP ligands towards iodoalkanes.

Nickel monocarbonyl species with Ni(I) and Ni(0) have been synthesized and fully characterized by employing an acriPNP-Ph pincer ligand having a -C(Ph)2- bridge moiety to tether two aromatic rings. To see the effect of the bridge moiety, these complexes were structurally compared with the previously studied nickel complexes supported by PNP and acriPNP-Me ligands and methylation of the nickel carbonyl species was particularly investigated. Since a Ni(I)-CO species is known to be one of the key intermediates during the C-C coupling reaction to give an acetyl species, according to the paramagnetic mechanism of acetyl coenzyme A synthase (ACS), their reactivity toward MeI has been examined. Methylation of a nickel(I)-CO species reveals enhanced C-C coupling when both acriPNP-Me and acriPNP-Ph ligands were used. According to spin density analysis calculated by density functional theory, all Ni(I)-CO species reveal similar spin density at nickel and the carbon atom of CO. X-ray crystallographic data suggest that the corresponding selectivity may be related to the steric influence. For both (acriPNP-Ph)Ni-CO (2) and (acriPNP-Me)Ni-CO (2'), the nickel(I) site is sterically well protected, leading to selective interaction with a methyl radical to give a nickel acyl product. Steric influence was marginally observed when an anionic {(acriPNP-R)Ni-CO}- (R = Me or Ph) species reacted with MeI. The corresponding C-C coupled product was also observed from the methylation of nickel(0)-CO species.

Accumulation of reactive carbonyl species in roots as the primary cause of salt stress‐induced growth retardation of Arabidopsis thaliana

AbstractSalt stress on plants induces an increase in reactive oxygen species (ROS), which then leads to the formation of reactive carbonyl species (RCS) such as acrolein and 4‐hydroxy‐(E)‐2‐nonenal (HNE), potent cytotoxins generated from lipid peroxides. We recently showed that salt‐stress treatment of Arabidopsis thaliana plants increased RCS levels, and exogenously added RCS‐scavenging chemicals alleviated the stress symptoms, indicating that RCS were responsible for the tissue damage in salt‐stressed plants. To obtain deeper insights into the role of RCS in stressed plants, we here analyzed changes in the levels of various RCS in the roots and shoots of A. thaliana. NaCl (90 mM) addition to the culture medium as a salt‐stress treatment caused growth inhibition and leaf chlorosis. Carbonyl analysis using HPLC revealed that the stress treatment induced a 2‐fold increase in the root levels of RCS, including acrolein, HNE and 4‐hydroxy‐(E)‐2‐hexenal (HHE). In the shoots, basal levels and stress‐induced increases of the RCS were lower than in roots. In the transgenic A. thaliana plants that overexpress the RCS‐scavenging enzyme 2‐alkenal reductase (AER) cDNA under the β‐estradiol (β‐ED)‐responsive promoter, salt stress induced less damage than in the wild‐type under β‐ED supplementation. The AER overexpression suppressed the stress‐induced increases in HNE, acrolein, HHE and (E)‐2‐hexenal in roots and in HNE in leaves, but not the ROS increase. These results suggest that the RCS increase in roots was the primary cause of salt‐induced damages. Enhancing RCS‐scavenging abilities, such as by AER overexpression, could be a new strategy to confer salt‐stress tolerance to plants.

Roles of Reactive Carbonyl Species (RCS) in Plant Response to Abiotic Stress.

Abiotic and biotic stress conditions lead to production of reactive carbonyl species (RCS) which are lipid peroxide derivatives and have detrimental effects on plant cells especially at high concentrations. There are several molecules that can be classified in RCS; among them, 4-hydroxy-(E)-2-nonenal (HNE) and acrolein are widely recognized and studied because of their toxicity. The toxicity mechanisms of RCS are well known in animals but their roles in plant systems especially signaling aspects in metabolism need to be addressed. This chapter focuses on the production mechanisms of RCS in plants as well as how plants scavenge and modify them to prevent irreversible damage in the cell. We aimed to get a comprehensive look at the literature to summarize the signaling roles of RCS in plant metabolism and their interaction with other signaling mechanisms such as highly recognized reactive oxygen species (ROS) signaling. Changing climate promotes more severe abiotic stress effects on plants which also decrease yield on the field. The effects of abiotic stress conditions on RCS metabolism are also gathered in this chapter including their signaling roles during abiotic stresses. Different methods of measuring RCS in plants are also presented in this chapter to draw more attention to the study of RCS metabolism in plants.

Glycation in the cardiomyocyte.

Glycation is a protein post-translational modification that can occur on lysine and arginine residues as a result of a non-enzymatic process known as the Maillard reaction. This modification is irreversible, so the only way it can be removed is by protein degradation and replacement. Small reactive carbonyl species, glyoxal and methylglyoxal, are the primary glycating agents and are elevated in several conditions associated with an increased risk of cardiovascular disease, including diabetes, rheumatoid arthritis, smoking, and aging. Thus, how protein glycation impacts the cardiomyocyte is of particular interest, to both understand how these conditions increase the risk of cardiovascular disease and how glycation might be targeted therapeutically. Glycation can affect the cardiomyocyte through extracellular mechanisms, including RAGE-based signaling, glycation of the extracellular matrix that modifies the mechanical environment, and signaling from the vasculature. Intracellular glycation of the cardiomyocyte can impact calcium handling, protein quality control and cell death pathways, as well as the cytoskeleton, resulting in a blunted contractility. While reducing protein glycation and its impact on the heart has been an active area of drug development, multiple clinical trials have had mixed results and these compounds have not been translated to the clinic-highlighting the challenges of modulating myocyte glycation. Here we will review protein glycation and its effects on the cardiomyocyte, therapeutic attempts to reverse these, and offer insight as to the future of glycation studies and patient treatment.

Emission characteristics of carbonyl compounds from open burning of typical subtropical biomass in South China

Open biomass burning (OBB) is one of the largest primary emission sources for atmospheric carbonyl compounds, key precursors for ozone and secondary organic aerosol pollution. To clarify the carbonyl emissions, the comprehensive characteristics of C1–C10 carbonyl compounds from open burning of seven typical subtropical biomass in China were investigated in this study, which included subtropical plants and agricultural residues. Total 27 carbonyl compounds were detected. The total EFs were 2824 mg kg−1 with 95% confidence interval (CI) [2418, 3322] for burning subtropical plants and 4080 mg kg−1 with 95% CI [3446, 4724] for burning agriculture residues, respectively. The EFs were 2–3 orders of magnitude larger than previous values in China. Aliphatic aldehydes were the largest group of carbonyl groups, with acetaldehyde, as the most abundant carbonyl species (about 30% contribution). Formaldehyde, acetone, acrolein, glyoxal, methylglyoxal, butanone, isovaleraldehyde, and m-tolualdehyde were also found to be abundant and varying with the types of biomass burnt. Formaldehyde emission ratios to acetonitrile and CO were lower than those in previous studies both for burning plants and agricultural residues. There were significant variabilities in the emission ratios and factors among different types of OBBs. Strong positive correlations were found between carbonyl emissions and CO emissions and water content in biomass; furthermore, total carbonyl concentrations measured in the flaming stage were higher than those in the smoldering one. This study provides important fundamental measurement data on carbonyl emissions from burning typical subtropical plants and agricultural residues, which will help improve the quality of emission inventories and better understand the potential impacts of OBB on regional air quality in southern China.

Theoretical basis validation and oxidative stress markers for cancer prevention clinical trials of aspirin

Aspirin, a nonsteroidal anti-inflammatory drug, has been proven effective in a clinical trial of carcinogenesis blockade. However, various modes of action have been reported for these effects. Thus, in this study, we aimed to present reasonable mode of actions as a proof of concept for human trials, especially trials for patients with familial adenomatous polyposis (FAP). Aspirin treatment at 1000 ppm inhibited intestinal tumorigenesis in FAP model Min mice. As a mode of action, aspirin regulated β-catenin signaling, inflammation, and oxidative stress both in vivo and in vitro. Furthermore, we examined novel markers predictive of aspirin treatment based on liquid biopsy. Here, we demonstrated that aspirin reduced the levels of reactive carbonyl species in the serum of Min mice. These data are expected to be of use for proof of concept of aspirin human trials and implied for the prediction of aspirin efficacy.

Impaired Detoxification of Trans, Trans-2,4-Decadienal, an Oxidation Product from Omega-6 Fatty Acids, Alters Insulin Signaling, Gluconeogenesis and Promotes Microvascular Disease.

Omega-6 fatty acids are the primary polyunsaturated fatty acids in most Western diets, while their role in diabetes remains controversial. Exposure of omega-6 fatty acids to an oxidative environment results in the generation of a highly reactive carbonyl species known as trans, trans-2,4-decadienal (tt-DDE). The timely and efficient detoxification of this metabolite, which has actions comparable to other reactive carbonyl species, such as 4-hydroxynonenal, acrolein, acetaldehyde, and methylglyoxal, is essential for disease prevention. However, the detoxification mechanism for tt-DDE remains elusive. In this study, the enzyme Aldh9a1b is identified as having a key role in the detoxification of tt-DDE. Loss of Aldh9a1b increased tt-DDE levels and resulted in an abnormal retinal vasculature and glucose intolerance in aldh9a1b-/- zebrafish. Transcriptomic and metabolomic analyses revealed that tt-DDE and aldh9a1b deficiency in larval and adult zebrafish induced insulin resistance and impaired glucose homeostasis. Moreover, alterations in hyaloid vasculature is induced by aldh9a1b knockout or by tt-DDE treatment can be rescued by the insulin receptor sensitizers metformin and rosiglitazone. Collectively, these results demonstrated that tt-DDE is the substrate of Aldh9a1b which causes microvascular damage and impaired glucose metabolism through insulin resistance.

Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation, followed by deleterious effects at the cellular and systemic levels, is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders, including metabolic syndrome, diabetes mellitus, and cardiovascular diseases. In this review, an interplay between pathways leading to MGO generation and scavenging is addressed in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases, are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

Inhibitory Potential of Carnosine and Aminoguanidine Towards Glycation and Fibrillation of Albumin: In-vitro and Simulation Studies.

Carnosine is beta-alanyl histidine, a dipeptide, endogenously produced in our body by the carnosine synthase enzyme. It is an antioxidant, thus protecting from the deleterious effect of advanced glycation end products (AGEs). Similarly, aminoguanidine (AG) also prevents AGEs formation by scavenging free radicals such as reactive oxygen species (ROS)/reactive carbonyl species (RCS). This study used experimental and computational techniques to perform a comparative analysis of carnosine and AG and their inhibiting properties against glycated human serum albumin (HSA). Fructose-mediated glycation of albumin produced fluorescent structures, such as pentosidine and malondialdehyde. These AGEs were significantly reduced by carnosine and AG. At 20mM, carnosine and AG quenches pentosidine fluorescence by 66% and 83%, respectively. A similar inhibitory effect was observed for malondialdehyde. Protein hydrophobicity and tryptophan fluorescence were restored in the presence of carnosine and AG. Aminoguanidine decreased fibrillation in HSA, while carnosine did not significantly affect aggregation/fibrillation. In addition, molecular docking study observed binding scores of -5.90kcal/mol and -2.59kcal/mol by HSA-aminoguanidine and HSA-carnosine complex, respectively. Aminoguanidine forms one conventional hydrogen bond with ARG A:10 and a salt bridge with ASP A:13, ASP A:259, ASP A:255, and ASP A:256 from the amine group. Similarly, carnosine forms only hydrogen bonds with GLU A:501 and GLN A:508 from the amine and hydroxy group. The root mean square deviation (RMSD) calculated from simulation studies was 1nm upto 70ns for the HSA-aminoguanidine complex and the spectrum of HSA-carnosine was significantly deviated and not stabilized. The superior inhibitory activity of aminoguanidine could be due to additional salt bridge bonding with albumin. Conclusively, aminoguanidine can be the better treatment choice for diabetes-associated neurological diseases.

Theanine in Tea: An Effective Scavenger of Single or Multiple Reactive Carbonyl Species at the Same Time.

Reactive carbonyl species (RCS) are generated during thermal food processing, and their accumulation in the body increases the risk of various chronic diseases. Herein, the RCS-scavenging ability of theanine, a unique nonproteinogenic amino acid, was evaluated in terms of the scavenging rate, reaction kinetics, and reaction pathway using LC-MS/MS. Three major products of theanine conjugated with acrolein (ACR) and glyoxal (GO) were prepared and identified using nuclear magnetic resonance. Thereafter, the simultaneous reactions of four types of RCS (namely, ACR, crotonaldehyde, methylglyoxal, and GO) with theanine were discussed in RCS-theanine and RCS-tea models. Under different reaction ratios, theanine could nonspecifically scavenge the four coexisting RCS by forming adducts with them. The amount of theanine-RCS adducts in green and black tea was more than that of catechin (epigallocatechin gallate, epigallocatechin, epicatechin gallate, and epicatechin)-RCS adducts despite the lower content of theanine than catechins. Thus, theanine, as a food additive and dietary supplement, could demonstrate new bioactivity as a promising RCS scavenger in food processing.

Validation of assays for measurement of oxidant compounds in saliva of pigs: Thiobarbituric acid reactive substances (TBARS), carbonyl, and reactive oxygen species (ROS)

Thiobarbituric acid reactive substances (TBARS), carbonyls and reactive oxygen species (ROS) are oxidant compounds that can provide useful information on the oxidative status. Pigs can be affected by oxidative stress in different situations including physiological conditions such as lactation and also in different diseases, and the measurement of these three analytes in saliva could be potentially useful as biomarkers of the redox status in this species. Assays for the measurement of TBARS and carbonyls by spectrophotometry and ROS by luminol-based chemiluminescence in pigs' saliva were analytically validated and were applied in saliva of pigs after an in vitro incubation with different doses of ascorbic acid (AA).All the assays showed a satisfactory analytical precision and accuracy. The 240 h-incubation of saliva samples with 60 mM of AA induced to an increased TBARS and carbonyls production. TBARS, carbonyls and ROS can be estimated in saliva of pigs by the assays validated in this report. In addition, these assays can detect changes in the concentration of these analytes associated to incubation of saliva samples with AA.

Inhalation toxicity of thermal transformation products formed from e-cigarette vehicle liquid using an in vitro lung model exposed at the Air–Liquid Interface

The increasing use of electronic nicotine delivery systems (ENDS), also known as e-cigarettes, has raised serious public health concerns, particularly regarding certain vaping product additives. The solvent carrier liquid, which consists of a mixture of propylene glycol (PG) and vegetable glycerine (VG), representing the main constituents of e-liquid formulations, have in contrast received little attention in health evaluations due to their apparent harmlessness when ingested; however, they can develop into potential lung hazards when heated, aerosolised and inhaled from ENDS with a user-defined heating profile. To assess the acute toxicity of the respirable aerosol, an effect-based in vitro testing strategy was applied in dependence of the heating power settings in ENDS. Human alveolar epithelial cells (A549) were exposed to vaping aerosol at the air–liquid interface (ALI), flanked by targeted chemical analyses of reactive carbonyl species. An exploratory, semi-automated in vitro exposure system provided evidence of a positive connection between vaporisation temperature and aerosol toxicity. Thermochemical transformation of the solvent leads to the formation of both cytotoxic and genotoxic substances that may disrupt lung homeostasis. Toxicity is therefore not limited to the presence of additives, as most harmful volatiles originate from the solvent itself, ultimately related to the device power output.

Cannflavins A and B with Anti-Ferroptosis, Anti-Glycation, and Antioxidant Activities Protect Human Keratinocytes in a Cell Death Model with Erastin and Reactive Carbonyl Species.

Precursors of advanced glycation endproducts, namely, reactive carbonyl species (RCSs), are aging biomarkers that contribute to cell death. However, the impact of RCSs on ferroptosis-an iron-dependent form of cell death-in skin cells remains unknown. Herein, we constructed a cellular model (with human keratinocyte; HaCaT cells) to evaluate the cytotoxicity of the combinations of RCSs (including glyoxal; GO and methyglyoxal; MGO) and erastin (a ferroptosis inducer) using bioassays (measuring cellular lipid peroxidation and iron content) and proteomics with sequential window acquisition of all theoretical mass spectra. Additionally, a data-independent acquisition approach was used to characterize RCSs' and erastin's molecular network including genes, canonical pathways, and upstream regulators. Using this model, we evaluated the cytoprotective effects of two dietary flavonoids including cannflavins A and B against RCSs and erastin-induced cytotoxicity in HaCaT cells. Cannflavins A and B (at 0.625 to 20 µM) inhibited ferroptosis by restoring the cell viability (by 56.6-78.6% and 63.8-81.1%) and suppressing cellular lipid peroxidation (by 42.3-70.2% and 28.8-63.6%), respectively. They also alleviated GO + erastin- or MGO + erastin-induced cytotoxicity by 62.2-67.6% and 56.1-69.3%, and 35.6-54.5% and 33.8-62.0%, respectively. Mechanistic studies supported that the cytoprotective effects of cannflavins A and B are associated with their antioxidant activities including free radical scavenging capacity and an inhibitory effect on glycation. This is the first study showing that cannflavins A and B protect human keratinocytes from RCSs + erastin-induced cytotoxicity, which supports their potential applications as dietary interventions for aging-related skin conditions.

Alleviating Drought Stress in Strawberry Plants: Unraveling the Role of Paclobutrazol as a Growth Regulator and Reducer of Oxidative Stress Induced by Reactive Oxygen and Carbonyl Species

Alleviating Drought Stress in Strawberry Plants: Unraveling the Role of Paclobutrazol as a Growth Regulator and Reducer of Oxidative Stress Induced by Reactive Oxygen and Carbonyl Species

Reducibility of Cu-zeolites and stability of Cu+ monocarbonyl adducts: Qualitative and quantitative relationships from MCR-XAS and DFT

A series of Cu-exchanged zeolites differing in framework topology and composition are studied through in situ X-ray Absorption Spectroscopy (XAS) to highlight differences in reducibility depending on the characteristics of the different samples. After reduction at high temperature in NH3, the samples are exposed to CO at 50 °C followed by a temperature-programmed desorption to study the different stability of carbonyl species forming on the Cu+ sites. Multivariate Curve Analysis applied to the XAS data allows extracting concentration profiles and pure spectral profiles on the species involved during several steps of the reaction. While all the samples are quantitatively reduced after treatment in NH3, the stability of the [Cu(CO)]+ sites shows a dependence on the topology of the materials. DFT calculations on possible sites occupied by Cu in the different frameworks are consistent with the stability trends observed experimentally and, together with isothermal volumetric CO adsorption data, confirm the particular instability of the Cu+-monocarbonyls formed in the CHA framework.

Synthetic 5-amino-6-D-ribitylaminouracil paired with inflammatory stimuli facilitates MAIT cell expansion in vivo.

Mucosal-associated invariant T (MAIT) cells are a population of innate-like T cells, which mediate host immunity to microbial infection by recognizing metabolite antigens derived from microbial riboflavin synthesis presented by the MHC-I-related protein 1 (MR1). Namely, the potent MAIT cell antigens, 5-(2-oxopropylideneamino)-6-D-ribitylaminouracil (5-OP-RU) and 5-(2-oxoethylideneamino)-6-D-ribitylaminouracil (5-OE-RU), form via the condensation of the riboflavin precursor 5-amino-6-D-ribitylaminouracil (5-A-RU) with the reactive carbonyl species (RCS) methylglyoxal (MG) and glyoxal (G), respectively. Although MAIT cells are abundant in humans, they are rare in mice, and increasing their abundance using expansion protocols with antigen and adjuvant has been shown to facilitate their study in mouse models of infection and disease. Here, we outline three methods to increase the abundance of MAIT cells in C57BL/6 mice using a combination of inflammatory stimuli, 5-A-RU and MG. Our data demonstrate that the administration of synthetic 5-A-RU in combination with one of three different inflammatory stimuli is sufficient to increase the frequency and absolute numbers of MAIT cells in C57BL/6 mice. The resultant boosted MAIT cells are functional and can provide protection against a lethal infection of Legionella longbeachae. These results provide alternative methods for expanding MAIT cells with high doses of commercially available 5-A-RU (± MG) in the presence of various danger signals.

Melatonin ameliorates histone modification disorders in mammalian aged oocytes by neutralizing the alkylation of HDAC1

Aging-associated histone modification changes in oocytes have been sporadically reported, but the underlying mechanisms remain elusive. Here, we systematically characterize multiple histone modifications in oocytes during aging. We find that maternal and postovulatory aging markedly alter the status of histone modifications, specifically H4K12ac and H3K4me3, in both mouse and porcine oocytes. Meanwhile, we identify a substantial reduction in HDAC1 (histone deacetylase 1) protein in aged oocytes, which contributes to the changes in H4K12ac and H3K4me3. Moreover, by employing methylglyoxal (MG) and site-directed mutagenesis, we demonstrate that the elevated reactive carbonyl species (RCS) level induces HDAC1 degradation, likely through attacking the cysteine residues, thereby influences histone modification state. Importantly, supplementation of melatonin not only prevents the loss of HDAC1 protein, but also partially corrects the H4K12ac and H3K4me3 status in aged oocytes. To sum up, this study established the link between redox disequilibrium and histone modification alterations during mammalian oocyte aging.

Sustainable and selective transfer hydrogenation using waste shrimp shell‐based tetrazene‐Ru (II) para‐cymene catalyst with ethanol as a hydrogen source

Sustainable chemical research emphasizes chitosan‐based catalysts and the need to explore the direct utilization of waste shrimp shells, whereas the use of ethanol as a hydrogen source in transfer hydrogenation is less explored due to its unfavorable redox potential, higher energy barriers, generation of reactive intermediates, and catalyst poising via metal carbonyl species or decarbonylation. Herein, we disclosed an efficient synthetic approach, conducted at ambient temperature, for surface functionalization of waste shrimp shells with 3‐(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐1,2,4,5‐tetrazine (DMPZ‐Tz) via nucleophilic substitution using 3,6‐bis(3,5‐dimethyl‐1H‐pyrazol‐1‐yl)‐1,2,4,5‐tetrazine (BDMPZ‐Tz). This method results in a color change and a 75% increase in surface nitrogen content, eliminating the need for multiple syntheses and harsh reaction conditions. We utilized the strong coordination property between DMPZ‐Tz and [Ru(p‐cym)Cl2]2/RuCl3.3H2O to develop ruthenium‐embedded transfer hydrogenation catalysts supported on shrimp shells. These catalysts were employed for the selective transfer hydrogenation of unsaturated carbonyl/aldehydes to saturated carbonyl/alcohols, utilizing ethanol as the hydrogen source and potassium carbonate as the base. The performance, selectivity, and reusability of the catalyst were thoroughly assessed through spectroscopic studies, in‐situ monitoring of the reaction progress, initial rate kinetics, and control experiments. The obtained results strongly indicated that the anchoring of DMPZ‐Tz played a crucial role in achieving superior performance compared with catalysts synthesized without it or utilizing its homogeneous counterparts. The catalyst exhibits efficient reactivity, selectivity, and broad substrate scope.

N-Nitrosation Based Fluorescence Turn-On Nitric Oxide Probe: Kinetic and Cell Imaging Studies.

Nitric oxide (NO) is a ubiquitous messenger molecule playing a key role in various physiological and pathological processes. However, producing a selective turn-on fluorescence response to NO is a challenging task due to (a) the very short half-life of NO (typically in the range of 0.1-10 s) in the biological milieu and (b) false positive responses to reactive carbonyl species (RCS) (e.g., dehydroascorbic acid and methylglyoxal etc.) and some other reactive oxygen/nitrogen species (ROS/RNS), especially with o-phenylenediamine (OPD) based fluorosensors. To avoid these limitations, NO sensors should be designed in such a way that they react spontaneously with NO to give turn-on response within the time frame of t1/2 (typically in the range of 0.1-10 s) of NO and λem in the visible wavelength along with good cell permeability to achieve biocompatibility. With these views in mind, a N-nitrosation based fluorescent sensor, NDAQ, has been developed that is highly selective to NO with ∼27-fold fluorescence enhancement at λem = 542 nm with high sensitivity (LOD = 7 ± 0.4 nM) and shorter response time, eliminating the interference of other reactive species (RCS/ROS/RNS). Furthermore, all the photophysical studies with NDAQ have been performed in 98% aqueous medium at physiological pH, indicating its good stability under physiological conditions. The kinetic assay illustrates the second-order dependency with respect to NO concentration and first-order dependency with respect to NDAQ concentration. The biological studies reveal the successful application of the probe to track both endogenous and exogenous NO in living organisms.

Saccharomyces cerevisiae DJ-1 paralogs maintain genome integrity through glycation repair of nucleic acids and proteins.

Reactive carbonyl species (RCS) such as methylglyoxal and glyoxal are potent glycolytic intermediates that extensively damage cellular biomolecules leading to genetic aberration and protein misfolding. Hence, RCS levels are crucial indicators in the progression of various pathological diseases. Besides the glyoxalase system, emerging studies report highly conserved DJ-1 superfamily proteins as critical regulators of RCS. DJ-1 superfamily proteins, including the human DJ-1, a genetic determinant of Parkinson's disease, possess diverse physiological functions paramount for combating multiple stressors. Although S. cerevisiae retains four DJ-1 orthologs (Hsp31, Hsp32, Hsp33, and Hsp34), their physiological relevance and collective requirement remain obscure. Here, we report for the first time that the yeast DJ-1 orthologs function as novel enzymes involved in the preferential scavenge of glyoxal and methylglyoxal, toxic metabolites, and genotoxic agents. Their collective loss stimulates chronic glycation of the proteome, and nucleic acids, inducing spectrum of genetic mutations and reduced mRNA translational efficiency. Furthermore, the Hsp31 paralogs efficiently repair severely glycated macromolecules derived from carbonyl modifications. Also, their absence elevates DNA damage response, making them vulnerable to various genotoxins. Interestingly, yeast DJ-1 orthologs preserve functional mitochondrial content, maintain ATP levels, and redistribute into mitochondria to alleviate the glycation damage of macromolecules. Together, our study uncovers a novel glycation repair pathway in S. cerevisiae and a possible neuroprotective mechanism of how hDJ-1 confers mitochondrial health during glycation toxicity.