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Science (New York, N.Y.) Jan 2022Atherosclerosis is an inflammatory disease of the artery walls and involves immune cells such as macrophages. Olfactory receptors (OLFRs) are G protein–coupled...
Atherosclerosis is an inflammatory disease of the artery walls and involves immune cells such as macrophages. Olfactory receptors (OLFRs) are G protein–coupled chemoreceptors that have a central role in detecting odorants and the sense of smell. We found that mouse vascular macrophages express the olfactory receptor and all associated trafficking and signaling molecules. Olfr2 detects the compound octanal, which activates the NLR family pyrin domain containing 3 (NLRP3) inflammasome and induces interleukin-1β secretion in human and mouse macrophages. We found that human and mouse blood plasma contains octanal, a product of lipid peroxidation, at concentrations sufficient to activate Olfr2 and the human ortholog olfactory receptor 6A2 (OR6A2). Boosting octanal levels exacerbated atherosclerosis, whereas genetic targeting of in mice significantly reduced atherosclerotic plaques. Our findings suggest that inhibiting OR6A2 may provide a promising strategy to prevent and treat atherosclerosis.
Topics: Adult; Aldehydes; Animals; Aorta; Atherosclerosis; Humans; Inflammasomes; Interleukin-1; Interleukin-1alpha; Interleukin-1beta; Lipid Peroxidation; Macrophages; Mice; Mice, Inbred C57BL; Middle Aged; NLR Family, Pyrin Domain-Containing 3 Protein; Oxidative Stress; Receptors, Odorant; Signal Transduction
PubMed: 35025664
DOI: 10.1126/science.abg3067 -
Biomolecules May 2022The discovery of aldehydes dates back to 1774 when Carl Wilhelm Scheele synthesized acetaldehyde [...].
The discovery of aldehydes dates back to 1774 when Carl Wilhelm Scheele synthesized acetaldehyde [...].
Topics: Acetaldehyde; Aldehyde Dehydrogenase; Aldehyde Dehydrogenase, Mitochondrial; Aldehydes
PubMed: 35740888
DOI: 10.3390/biom12060763 -
Chemical Research in Toxicology Jul 2023Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of... (Review)
Review
Aldehydes are widespread in the environment, with multiple sources such as food and beverages, industrial effluents, cigarette smoke, and additives. The toxic effects of exposure to several aldehydes have been observed in numerous studies. At the molecular level, aldehydes damage DNA, cross-link DNA and proteins, lead to lipid peroxidation, and are associated with increased disease risk including cancer. People genetically predisposed to aldehyde sensitivity exhibit severe health outcomes. In various diseases such as Fanconi's anemia and Cockayne syndrome, loss of aldehyde-metabolizing pathways in conjunction with defects in DNA repair leads to widespread DNA damage. Importantly, aldehyde-associated mutagenicity is being explored in a growing number of studies, which could offer key insights into how they potentially contribute to tumorigenesis. Here, we review the genotoxic effects of various aldehydes, focusing particularly on the DNA adducts underlying the mutagenicity of environmentally derived aldehydes. We summarize the chemical structures of the aldehydes and their predominant DNA adducts, discuss various methodologies, and , commonly used in measuring aldehyde-associated mutagenesis, and highlight some recent studies looking at aldehyde-associated mutation signatures and spectra. We conclude the Review with a discussion on the challenges and future perspectives of investigating aldehyde-associated mutagenesis.
Topics: Humans; Aldehydes; DNA Adducts; DNA Damage; DNA Repair; Mutagens; DNA
PubMed: 37363863
DOI: 10.1021/acs.chemrestox.3c00045 -
Frontiers in Public Health 2022Environmental pollution sources may play a key role in the pathogenesis of nephrolithiasis, although the link between environmental aldehyde exposure and the incidence...
Environmental pollution sources may play a key role in the pathogenesis of nephrolithiasis, although the link between environmental aldehyde exposure and the incidence of nephrolithiasis is unclear. The researchers in this study set out to see whether adult kidney stone formation was linked to environmental aldehydes. We examined data from 10,175 adult participants over the age of 20 who took part in the 2013-2014 National Health and Nutrition Examination Survey (NHANES), which was a cross-sectional research. A logistic regression model was employed in this work to examine the relationship between aldehyde exposure and kidney stones, machine learning was utilized to predict the connection of different parameters with the development of kidney stones, and a subgroup analysis was performed to identify sensitive groups. After controlling for all confounding variables, the results revealed that isopentanaldehyde, benzaldehyde, and hexanaldehyde were risk factors for kidney stone formation, with odds ratio (OR) of 2.47, 1.12, and 1.17, respectively, and 95 percent confidence intervals (95% CI) of 1.15-5.34, 1.02-1.22, and 1.00-1.36. Kidney stones may be a result of long-term exposure to aldehydes, which may cause them to form. Environmental pollution-related aldehyde exposure might give a novel notion and direction for future study into the process of kidney stone production, even if the cause is yet unknown.
Topics: Adult; Humans; Nutrition Surveys; Benzaldehydes; Cross-Sectional Studies; Kidney Calculi; Aldehydes
PubMed: 36299743
DOI: 10.3389/fpubh.2022.978338 -
PeerJ 2022Plant aldehyde oxidases (AOs) are multi-functional enzymes, and they could oxidize abscisic aldehyde into ABA (abscisic acid) or indole acetaldehyde into IAA... (Review)
Review
Plant aldehyde oxidases (AOs) are multi-functional enzymes, and they could oxidize abscisic aldehyde into ABA (abscisic acid) or indole acetaldehyde into IAA (indoleacetic acid) as the last step, respectively. AOs can be divided into four groups based on their biochemical and physiological functions. In this review, we summarized the recent studies about AOs in plants including the motif information, biochemical, and physiological functions. Besides their role in phytohormones biosynthesis and stress response, AOs could also involve in reactive oxygen species homeostasis, aldehyde detoxification and stress tolerance.
Topics: Aldehyde Oxidase; Plant Growth Regulators; Abscisic Acid; Aldehydes; Reactive Oxygen Species
PubMed: 35356472
DOI: 10.7717/peerj.13119 -
Applied and Environmental Microbiology Mar 2015Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known... (Review)
Review
Aldehydes are a class of chemicals with many industrial uses. Several aldehydes are responsible for flavors and fragrances present in plants, but aldehydes are not known to accumulate in most natural microorganisms. In many cases, microbial production of aldehydes presents an attractive alternative to extraction from plants or chemical synthesis. During the past 2 decades, a variety of aldehyde biosynthetic enzymes have undergone detailed characterization. Although metabolic pathways that result in alcohol synthesis via aldehyde intermediates were long known, only recent investigations in model microbes such as Escherichia coli have succeeded in minimizing the rapid endogenous conversion of aldehydes into their corresponding alcohols. Such efforts have provided a foundation for microbial aldehyde synthesis and broader utilization of aldehydes as intermediates for other synthetically challenging biochemical classes. However, aldehyde toxicity imposes a practical limit on achievable aldehyde titers and remains an issue of academic and commercial interest. In this minireview, we summarize published efforts of microbial engineering for aldehyde synthesis, with an emphasis on de novo synthesis, engineered aldehyde accumulation in E. coli, and the challenge of aldehyde toxicity.
Topics: Aldehydes; Escherichia coli; Metabolic Engineering; Microbial Viability
PubMed: 25576610
DOI: 10.1128/AEM.03319-14 -
International Journal of Molecular... May 2021The production of aldehydes, highly reactive and toxic chemicals, brings specific challenges to biocatalytic processes. Absence of natural accumulation of aldehydes in... (Review)
Review
The production of aldehydes, highly reactive and toxic chemicals, brings specific challenges to biocatalytic processes. Absence of natural accumulation of aldehydes in microorganisms has led to a combination of in vitro and in vivo strategies for both, bulk and fine production. Advances in genetic and metabolic engineering and implementation of computational techniques led to the production of various enzymes with special requirements. Cofactor synthesis, post-translational modifications and structure engineering are applied to prepare active enzymes for one-step or cascade reactions. This review presents the highlights in biocatalytical production of aldehydes with the potential to shape future industrial applications.
Topics: Aldehydes; Biocatalysis; Biosensing Techniques; Enzymes; Ligands; Metabolic Engineering
PubMed: 34066641
DOI: 10.3390/ijms22094949 -
Carbohydrate Polymers Aug 2018From the suspensions of cellulose nanocrystals (CNCs) derived from cotton and flax by acidic hydrolysis, transparent and smooth films were produced with different...
From the suspensions of cellulose nanocrystals (CNCs) derived from cotton and flax by acidic hydrolysis, transparent and smooth films were produced with different plasticizers and an amino-aldehyde based cross-linking agent in a wide composition range by a simultaneous casting and wet cross-linking process. The effect of cross-linker concentration on the optical and tensile properties and on the morphology of CNC films was investigated by various measurements. The interaction of films with liquid water and water vapour was also characterized by water sorption and water contact angle as well as performing a sinking test. Cross-linking improved the transparency, reduced the porosity and surface free energy, and prevented the delamination of CNC films in water at a concentration of 10% or higher. The surface of CNC films is basic in character and has an electron donor property. The CNC/amino-aldehyde films had a high tensile strength (45 MPa) and modulus (11 GPa).
Topics: Adsorption; Aldehydes; Biocompatible Materials; Cellulose; Cross-Linking Reagents; Nanoparticles; Water
PubMed: 29801858
DOI: 10.1016/j.carbpol.2018.04.025 -
American Journal of Physiology. Cell... Oct 2016In this perspective, we summarize and discuss critical advancements in the study of 4-hydroxy-2-nonenal (4-HNE) as it relates to diseases and clinical complications... (Review)
Review
In this perspective, we summarize and discuss critical advancements in the study of 4-hydroxy-2-nonenal (4-HNE) as it relates to diseases and clinical complications either caused or exacerbated by oxidative stress. Since its identification in 1980, 4-HNE has been extensively studied with an emphasis on its formation, its role in pathology, and its targets. As a reactive aldehyde, and a product of lipid peroxidation, studies corroborate its ability to disrupt signal transduction and protein activity, as well as induce inflammation and trigger cellular apoptosis in conditions of oxidative stress. Notably, we discuss the role of natural enzymes involved in the regulation of 4-HNE, and how they can be applied to its detoxification in various physiological conditions.
Topics: Aldehydes; Animals; Apoptosis; Humans; Lipid Peroxidation; Oxidative Stress; Signal Transduction
PubMed: 27385721
DOI: 10.1152/ajpcell.00101.2016 -
Molecules (Basel, Switzerland) Feb 2023The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists' interest in the field. It... (Review)
Review
The Ugi four-component reaction (Ugi-4CR) undoubtedly is the most prominent multicomponent reaction (MCRs) that has sparked organic chemists' interest in the field. It has been widely used in the synthesis of diverse heterocycle molecules such as potential drugs, natural product analogs, pseudo peptides, macrocycles, and functional materials. The Ugi-4CRs involve the use of an amine, an aldehyde or ketone, an isocyanide, and a carboxylic acid to produce an α-acetamido carboxamide derivative, which has significantly advanced the field of isocyanide-based MCRs. The so-called intermediate nitrilium ion could be trapped by a nucleophile such as azide, -hydroxyphthalimide, thiol, saccharin, phenol, water, and hydrogen sulfide instead of the original carboxylic acid to allow for a wide variety of Ugi-type reactions to occur.β In addition to isocyanide, there are alternative reagents for the other three components: amine, isocyanide, and aldehyde or ketone. All these alternative components render the Ugi reaction an aptly diversity-oriented synthesis of a myriad of biologically active molecules and complex scaffolds. Consequently, this review will delve deeper into alternative components used in the Ugi MCRs, particularly over the past ten years.
Topics: Peptides; Amines; Cyanides; Carboxylic Acids; Aldehydes
PubMed: 36838630
DOI: 10.3390/molecules28041642