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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 -
Heart Rhythm Sep 2022Cardiac arrhythmia is a common cardiovascular disease that leads to considerable economic burdens and significant global public health challenges. Despite the remarkable... (Review)
Review
Cardiac arrhythmia is a common cardiovascular disease that leads to considerable economic burdens and significant global public health challenges. Despite the remarkable progress made in recent decades, antiarrhythmic therapy remains suboptimal. Aldehyde dehydrogenase 2 (ALDH2), a critical detoxifying enzyme, catalyzes toxic aldehydes and protects individuals from damage caused by oxidative stress. Accumulating evidence has demonstrated that ALDH2 activation has potential antiarrhythmic benefits. The correlation between ALDH2 deficiency and arrhythmogenesis has been widely recognized. In this review, we summarize recent research on the potential role of ALDH2 activation and antiarrhythmic protection, as well as the role played by the ALDH2∗2 polymorphism (rs671) in promoting arrhythmic risk. Additionally, we discuss important new findings illustrating the use of ALDH2 activators, which may prove to be promising antiarrhythmic therapy agents.
Topics: Aldehyde Dehydrogenase, Mitochondrial; Aldehydes; Arrhythmias, Cardiac; Humans; Oxidative Stress; Polymorphism, Genetic
PubMed: 35568135
DOI: 10.1016/j.hrthm.2022.05.008 -
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 -
Science Advances Jul 2023The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to target molecules that are buried within specialized...
The gold-standard fixative for immunohistochemistry is 4% formaldehyde; however, it limits antibody access to target molecules that are buried within specialized neuronal components, such as ionotropic receptors at the postsynapse and voltage-gated ion channels at the axon initial segment, often requiring additional antigen-exposing techniques to detect their authentic signals. To solve this problem, we used glyoxal, a two-carbon atom di-aldehyde. We found that glyoxal fixation greatly improved antibody penetration and immunoreactivity, uncovering signals for buried molecules by conventional immunohistochemical procedures at light and electron microscopic levels. It also enhanced immunosignals of most other molecules, which are known to be detectable in formaldehyde-fixed sections. Furthermore, we unearthed several specific primary antibodies that were once judged to be unusable in formaldehyde-fixed tissues, allowing us to successfully localize so far controversial synaptic adhesion molecule Neuroligin 1. Thus, glyoxal is a highly effective fixative for immunostaining, and a side-by-side comparison of glyoxal and formaldehyde fixation is recommended for routine immunostaining in neuroscience research.
Topics: Fixatives; Tissue Fixation; Glyoxal; Formaldehyde; Antigens; Antibodies
PubMed: 37450597
DOI: 10.1126/sciadv.adf7084 -
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 -
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 -
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 -
Biomolecules Jan 20224-hydroxy-2,3-trans-nonenal (CHO), also known as 4-hydroxy--nonenal (CHO; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the... (Review)
Review
4-hydroxy-2,3-trans-nonenal (CHO), also known as 4-hydroxy--nonenal (CHO; HNE) is an α,β-unsaturated hydroxyalkenal. HNE is a major aldehyde, formed in the peroxidation process of ω-6 polyunsaturated fatty acids (ω-6 PUFAs), such as linoleic and arachidonic acid. HNE is not only harmful but also beneficial. In the 1980s, the HNE was regarded as a "toxic product of lipid peroxidation" and the "second toxic messenger of free radicals". However, already at the beginning of the 21st century, HNE was perceived as a reliable marker of oxidative stress, growth modulating factor and signaling molecule. Many literature data also indicate that an elevated level of HNE in blood plasma and cells of the animal and human body is observed in the course of many diseases, including cancer. On the other hand, it is currently proven that cancer cells divert to apoptosis if they are exposed to supraphysiological levels of HNE in the cancer microenvironment. In this review, we briefly summarize the current knowledge about the biological properties of HNE.
Topics: Aldehydes; Animals; Arachidonic Acid; Fatty Acids, Unsaturated; Lipid Peroxidation; Oxidative Stress
PubMed: 35053293
DOI: 10.3390/biom12010145