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Nature Reviews. Cardiology Jul 2023Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating... (Review)
Review
Aldehyde dehydrogenase 2 (ALDH2) is a mitochondrial enzyme involved in the detoxification of alcohol-derived acetaldehyde and endogenous aldehydes. The inactivating ALDH2 rs671 polymorphism, present in up to 8% of the global population and in up to 50% of the East Asian population, is associated with increased risk of cardiovascular conditions such as coronary artery disease, alcohol-induced cardiac dysfunction, pulmonary arterial hypertension, heart failure and drug-induced cardiotoxicity. Although numerous studies have attributed an accumulation of aldehydes (secondary to alcohol consumption, ischaemia or elevated oxidative stress) to an increased risk of cardiovascular disease (CVD), this accumulation alone does not explain the emerging protective role of ALDH2 rs671 against ageing-related cardiac dysfunction and the development of aortic aneurysm or dissection. ALDH2 can also modulate risk factors associated with atherosclerosis, such as cholesterol biosynthesis and HDL biogenesis in hepatocytes and foam cell formation and efferocytosis in macrophages, via non-enzymatic pathways. In this Review, we summarize the basic biology and the clinical relevance of the enzymatic and non-enzymatic, tissue-specific roles of ALDH2 in CVD, and discuss the future directions in the research and development of therapeutic strategies targeting ALDH2. A thorough understanding of the complex roles of ALDH2 in CVD will improve the diagnosis, management and prognosis of patients with CVD who harbour the ALDH2 rs671 polymorphism.
Topics: Humans; Cardiovascular Diseases; Aldehyde Dehydrogenase, Mitochondrial; Polymorphism, Genetic; Coronary Artery Disease; Aldehydes; Ethanol
PubMed: 36781974
DOI: 10.1038/s41569-023-00839-5 -
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 -
Journal of Chromatography. A Aug 2022Analytical derivatization is a technique that alters the structure of an analyte and produces a product more suitable for analysis. While this process can be... (Review)
Review
Analytical derivatization is a technique that alters the structure of an analyte and produces a product more suitable for analysis. While this process can be time-consuming and add reagents to the procedure, it can also facilitate the isolation of the analyte(s), enhance analytes' stability, improve separation and sensitivity, and reduce matrix interferences. Since derivatization is a functional group analysis, it improves selectivity by separating reactive from neutral compounds during sample preparation. This technique introduces detector-orientated tags into analytes that lack suitable physicochemical properties for detection at low concentrations. Notably, many regulatory bodies, especially those in the environmental field, require these characteristics in analytical methods. This review focuses on note-worthy analytical derivatization methods employed in environmental analyses with functional groups, phenol, carboxylic acid, aldehyde, ketone, and thiol in aqueous, soil, and atmospheric sample matrices. Both advantages and disadvantages of analytical derivatization techniques are discussed. In addition, we discuss the future directions of analytical derivatization methods in environmental analysis and the potential challenges.
Topics: Aldehydes; Carboxylic Acids; Indicators and Reagents; Ketones; Phenols
PubMed: 35901668
DOI: 10.1016/j.chroma.2022.463348 -
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 -
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 -
Free Radical Research Apr 2021Cholesterol is an essential component of mammalian plasma membranes. Alterations in sterol metabolism or oxidation have been linked to various pathological conditions,... (Review)
Review
Cholesterol is an essential component of mammalian plasma membranes. Alterations in sterol metabolism or oxidation have been linked to various pathological conditions, including cardiovascular diseases, cancer, and neurodegenerative disorders. Unsaturated sterols are vulnerable to oxidation induced by singlet oxygen and other reactive oxygen species. This process yields reactive sterol oxidation products, including hydroperoxides, epoxides as well as aldehydes. These oxysterols, in particular those with high electrophilicity, can modify nucleophilic sites in biomolecules and affect many cellular functions. Here, we review the generation and measurement of reactive sterol oxidation products with emphasis on cholesterol hydroperoxides and aldehyde derivatives (electrophilic oxysterols) and their effects on protein modifications.
Topics: Aldehydes; Animals; Cholesterol; Humans; Oxysterols; Proteins
PubMed: 33494620
DOI: 10.1080/10715762.2021.1879387 -
Archives of Biochemistry and Biophysics Mar 20214-hydroxynonenal (HNE, 4-hydroxy-2-nonenal) is a primary α,β-unsaturated aldehyde product of lipid peroxidation. The accumulation of HNE increases with aging and the... (Review)
Review
4-hydroxynonenal (HNE, 4-hydroxy-2-nonenal) is a primary α,β-unsaturated aldehyde product of lipid peroxidation. The accumulation of HNE increases with aging and the mechanisms are mainly attributable to increased oxidative stress and decreased capacity of HNE elimination. In this review article, we summarize the studies on age-related change of HNE concentration and alteration of HNE metabolizing enzymes (GCL, GST, ALDHs, aldose reductase, and 20S-proteasome), and discuss potential mechanism of age-related decrease in HNE-elimination capacity by focusing on Nrf2 redox signaling.
Topics: Aging; Aldehydes; Animals; Humans; Oxidative Stress; Oxidoreductases; Signal Transduction
PubMed: 33417945
DOI: 10.1016/j.abb.2020.108749