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International Journal of Molecular... Aug 2023The aging of the global population has necessitated the identification of effective anti-aging technologies based on scientific evidence. Polyamines (putrescine,...
The aging of the global population has necessitated the identification of effective anti-aging technologies based on scientific evidence. Polyamines (putrescine, spermidine, and spermine) are essential for cell growth and function. Age-related reductions in polyamine levels have been shown to be associated with reduced cognitive and physical functions. We have previously found that the expression of spermine oxidase (SMOX) increases with age; however, the relationship between SMOX expression and cellular senescence remains unclear. Therefore, we investigated the relationship between increased SMOX expression and cellular senescence using human-liver-derived HepG2 cells. Intracellular spermine levels decreased and spermidine levels increased with the serial passaging of cells (aged cells), and aged cells showed increased expression of SMOX. The levels of acrolein-conjugated protein, which is produced during spermine degradation, also increases. Senescence-associated β-gal activity was increased in aged cells, and the increase was suppressed by MDL72527, an inhibitor of acetylpolyamine oxidase (AcPAO) and SMOX, both of which are enzymes that catalyze polyamine degradation. DNA damage accumulated in aged cells and MDL72527 reduced DNA damage. These results suggest that the SMOX-mediated degradation of spermine plays an important role in cellular senescence. Our results demonstrate that cellular senescence can be controlled by inhibiting spermine degradation using a polyamine-catabolizing enzyme inhibitor.
Topics: Humans; Spermidine; Spermine; Cellular Senescence; Aging; Polyamines
PubMed: 37686212
DOI: 10.3390/ijms241713397 -
Molecules (Basel, Switzerland) May 2024High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the...
High concentrations of acrolein (2-propenal) are found in polluted air and cigarette smoke, and may also be generated endogenously. Acrolein is also associated with the induction and progression of many diseases. The high reactivity of acrolein towards the thiol and amino groups of amino acids may cause damage to cell proteins. Acrolein may be responsible for the induction of oxidative stress in cells. We hypothesized that acrolein may contribute to the protein damage in erythrocytes, leading to the disruption of the structure of cell membranes. The lipid membrane fluidity, membrane cytoskeleton, and osmotic fragility were measured for erythrocytes incubated with acrolein for 24 h. The levels of thiol, amino, and carbonyl groups were determined in cell membrane and cytosol proteins. The level of non-enzymatic antioxidant potential (NEAC) and TBARS was also measured. The obtained research results showed that the exposure of erythrocytes to acrolein causes changes in the cell membrane and cytosol proteins. Acrolein stiffens the cell membrane of erythrocytes and increases their osmotic sensitivity. Moreover, it has been shown that erythrocytes treated with acrolein significantly reduce the non-enzymatic antioxidant potential of the cytosol compared to the control.
Topics: Acrolein; Cytosol; Erythrocytes; Humans; Erythrocyte Membrane; Oxidative Stress; Antioxidants; Membrane Proteins; Cell Membrane; Membrane Fluidity; Osmotic Fragility
PubMed: 38893395
DOI: 10.3390/molecules29112519 -
Free Radical Biology & Medicine Oct 2023Acrolein, which is the most reactive aldehyde, is a byproduct of lipid peroxidation in a hypoxic environment. Acrolein has been shown to form acrolein-cysteine bonds,...
Acrolein, which is the most reactive aldehyde, is a byproduct of lipid peroxidation in a hypoxic environment. Acrolein has been shown to form acrolein-cysteine bonds, resulting in functional changes in proteins and immune effector cell suppression. Neutrophils are the most abundant immune effector cells in circulation in humans. In the tumor microenvironment, proinflammatory tumor-associated neutrophils (TANs), which are termed N1 neutrophils, exert antitumor effects via the secretion of cytokines, while anti-inflammatory neutrophils (N2 neutrophils) support tumor growth. Glioma is characterized by significant tissue hypoxia, immune cell infiltration, and a highly immunosuppressive microenvironment. In glioma, neutrophils exert antitumor effects early in tumor development but gradually shift to a tumor-supporting role as the tumor develops. However, the mechanism of this anti-to protumoral switch in TANs remains unclear. In this study, we found that the production of acrolein in glioma cells under hypoxic conditions inhibited neutrophil activation and induced an anti-inflammatory phenotype by directly reacting with Cys310 of AKT and inhibiting AKT activity. A higher percentage of cells expressing acrolein adducts in tumor tissue are associated with poorer prognosis in glioblastoma patients. Furthermore, high-grade glioma patients have increased serum acrolein levels and impaired neutrophil functions. These results suggest that acrolein suppresses neutrophil function and contributes to the switch in the neutrophil phenotype in glioma.
Topics: Humans; Acrolein; Neutrophils; Proto-Oncogene Proteins c-akt; Glioblastoma; Anti-Inflammatory Agents; Tumor Microenvironment
PubMed: 37414347
DOI: 10.1016/j.freeradbiomed.2023.06.027 -
BJU International Dec 2023Haemorrhagic cystitis (HC) is characterised by persistent haematuria and lower urinary tract symptoms following radiotherapy or chemotherapy. Its pathogenesis is poorly... (Review)
Review
Haemorrhagic cystitis (HC) is characterised by persistent haematuria and lower urinary tract symptoms following radiotherapy or chemotherapy. Its pathogenesis is poorly understood but thought to be related to acrolein toxicity following chemotherapy or fibrosis/vascular remodelling after radiotherapy. There is no standard of care for patients with HC, although existing strategies including fulguration, hyperbaric oxygen therapy, botulinum toxin A, and other intravesical therapies have demonstrated short-term efficacy in cohort studies. Novel agents including liposomal tacrolimus are promising targets for further research. This review summarises the incidence and pathogenesis of HC as well as current evidence supporting its different management strategies.
Topics: Humans; Hemorrhage; Cystitis; Hematuria; Cohort Studies; Hyperbaric Oxygenation
PubMed: 37501638
DOI: 10.1111/bju.16140 -
Cardiovascular Research Oct 2023Electronic cigarette use has grown exponentially in recent years, and while their popularity has increased, the long-term effects on the heart are yet to be fully... (Review)
Review
Electronic cigarette use has grown exponentially in recent years, and while their popularity has increased, the long-term effects on the heart are yet to be fully studied and understood. Originally designed as devices to assist with those trying to quit traditional combustible cigarette use, their popularity has attracted use by teens and adolescents who traditionally have not smoked combustible cigarettes. Acute effects on the heart have been shown to be similar to traditional combustible cigarettes, including increased heart rate and blood pressure. The main components of electronic cigarettes that contribute to these arrhythmic effects are found in the e-liquid that is aerosolized and inhaled, comprised of nicotine, flavourings, and a combination of vegetable glycerin (VG) and propylene glycol (PG). Nicotine can potentially induce both ventricular and atrial arrhythmogenesis, with both the atrial and ventricular effects resulting from the interactions of nicotine and the catecholamines they release via potassium channels. Atrial arrhythmogenesis, more specifically atrial fibrillation, can also occur due to structural alterations, which happens because of nicotine downregulating microRNAs 133 and 590, both post-transcriptional growth factor repressors. Liquid flavourings and the combination of PG and VG can possibly lead to arrhythmic events by exposing users to acrolein, an aldehyde that stimulates TRPA1 that in turn causes a change towards sympathetic activation and autonomic imbalance. The design of these electronic delivery devices is constantly changing; therefore, it has proven extremely difficult to study the long-term effects on the heart caused by electronic cigarettes but will be important to understand given their rising popularity. The arrhythmic effects of electronic cigarettes appear similar to traditional cigarettes as well; however, a comprehensive review has not been compiled and is the focus of this article.
Topics: Adolescent; Humans; Nicotine; Electronic Nicotine Delivery Systems; Atrial Fibrillation; Propylene Glycol; Glycerol
PubMed: 37517059
DOI: 10.1093/cvr/cvad113 -
Chemosphere Oct 2023Evidence on liver injury and non-alcoholic fatty liver disease (NAFLD) from volatile organic compounds (VOCs) exposure is insufficient. A cross-sectional study including...
Single-chemical and mixture effects of multiple volatile organic compounds exposure on liver injury and risk of non-alcoholic fatty liver disease in a representative general adult population.
Evidence on liver injury and non-alcoholic fatty liver disease (NAFLD) from volatile organic compounds (VOCs) exposure is insufficient. A cross-sectional study including 3011 US adults from the National Health and Nutrition Examination Survey was conducted to explore the associations of urinary exposure biomarkers (EBs) for 13 VOCs (toluene, xylene, ethylbenzene, styrene, acrylamide, N,N-dimethylformamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, propylene oxide, and 1-bromopropane) with liver injury biomarkers and the risk of NAFLD by performing single-chemical (survey weight regression) and mixture (Bayesian kernel machine regression [BKMR] and weighted quantile sum [WQS]) analyses. We found significant positive associations of EBs for toluene and 1-bromopropane with alanine aminotransferase (ALT), EBs for toluene, crotonaldehyde, and 1,3-butadiene with asparate aminotransferase (AST), EBs for 1,3-butadiene and cyanide with alkaline phosphatase (ALP), EBs for xylene and cyanide with hepamet fibrosis score (HFS), EBs for the total 13 VOCs (except propylene oxide) with United States fatty liver index (USFLI), and EBs for xylene, N,N-dimethylformamide, acrolein, crotonaldehyde, and acrylonitrile with NALFD; and significant inverse associations of EBs for ethylbenzene, styrene, acrylamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, and propylene oxide with total bilirubin, EBs for ethylbenzene, styrene, acrylamide, acrolein, 1,3-butadiene, acrylonitrile, and cyanide with albumin (ALB), EBs for ethylbenzene, styrene, acrylamide, N,N-dimethylformamide, acrolein, crotonaldehyde, 1,3-butadiene, acrylonitrile, cyanide, and propylene oxide with total protein (TP), and EB for 1-bromopropane with AST/ALT (all P-FDR<0.05). In BKMR and WQS, the mixture of VOC-EBs was significantly positively associated with ALT, AST, ALP, HFS, USFLI, and the risk of NAFLD, while significantly inversely associated with TBIL, ALB, TP, and AST/ALT. VOCs exposure was associated with liver injury and increased risk of NAFLD in US adults. These findings highlight that great attention should be paid to the potential risk of liver health damage from VOCs exposure.
Topics: Humans; Adult; United States; Non-alcoholic Fatty Liver Disease; Volatile Organic Compounds; Xylenes; Nutrition Surveys; Acrolein; Acrylonitrile; Bayes Theorem; Cross-Sectional Studies; Dimethylformamide; Toluene; Biomarkers; Acrylamides; Styrenes
PubMed: 37553041
DOI: 10.1016/j.chemosphere.2023.139753 -
International Journal of Molecular... Jul 2023Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of...
Transient receptor potential ankyrin 1 (TRPA1) is a nonselective ion channel implicated in thermosensation and inflammatory pain. It has been reported that expression of the TRPA1 channel is induced by cigarette smoke extract. Acrolein found in cigarette smoke is highly toxic and known as an agonist of the TRPA1 channel. However, the role of TRPA1 in the cytotoxicity of acrolein remains unclear. Here, we investigated whether the TRPA1 channel is involved in the cytotoxicity of acrolein in human lung cancer A549 cells. The IC of acrolein in A549 cells was 25 μM, and acrolein toxicity increased in a concentration- and time-dependent manner. When the effect of acrolein on TRPA1 expression was examined, the expression of TRPA1 in A549 cells was increased by treatment with 50 μM acrolein for 24 h or 500 μM acrolein for 30 min. AP-1, a transcription factor, was activated in the cells treated with 50 μM acrolein for 24 h, while induction of NF-κB and HIF-1α was observed in the cells treated with 500 μM acrolein for 30 min. These results suggest that acrolein induces TRPA1 expression by activating these transcription factors. Overexpression of TRPA1 in A549 cells increased acrolein sensitivity and the level of protein-conjugated acrolein (PC-Acro), while knockdown of TRPA1 in A549 cells or treatment with a TRPA1 antagonist caused tolerance to acrolein. These findings suggest that acrolein induces the TRPA1 channel and that an increase in TRPA1 expression promotes the cytotoxicity of acrolein.
Topics: Humans; Transient Receptor Potential Channels; Acrolein; TRPA1 Cation Channel; Ankyrins; Lung Neoplasms; Cytoskeletal Proteins
PubMed: 37511605
DOI: 10.3390/ijms241411847 -
Redox Biology Jul 2023Psoriasis, one of the most frequent immune-mediated skin diseases, is manifested by numerous psoriatic lessons on the skin caused by excessive proliferation and... (Review)
Review
Psoriasis, one of the most frequent immune-mediated skin diseases, is manifested by numerous psoriatic lessons on the skin caused by excessive proliferation and keratinization of epidermal cells. These disorders of keratinocyte metabolism are caused by a pathological interaction with the cells of the immune system, including lymphocytes, which in psoriasis are also responsible for systemic inflammation. This is accompanied by oxidative stress, which promotes the formation of lipid peroxidation products, including reactive aldehydes and isoprostanes, which are additional pro-inflammatory signaling molecules. Therefore, the presented review is focused on highlighting changes that occur during psoriasis development at the level of lipid peroxidation products, including 4-hydroxynonenal, 4-oxononenal, malondialdehyde, and acrolein, and their influence on protein structures. Furthermore, we will examine inducing agents of cellular functioning, as well as intercellular signaling. These lipid peroxidation products can form adducts with a variety of proteins with different functions in the body, including proteins within skin cells and cells of the immune system. This is especially true in autoimmune diseases such as psoriasis. For example, these changes concern proteins involved in maintaining redox homeostasis or pro-inflammatory signaling. Therefore, the formation of such adducts should attract attention, especially during the design of preventive cosmetics or anti-psoriasis therapies.
Topics: Humans; Lipid Peroxidation; Aldehydes; Malondialdehyde; Psoriasis; Proteins; Oxidation-Reduction
PubMed: 37150149
DOI: 10.1016/j.redox.2023.102729 -
Biochemical and Biophysical Research... Dec 2023Under the exposure of lipids to reactive oxygen species (ROS), lipid peroxidation proceeds non-enzymatically and generates an extremely heterogeneous mixture of reactive... (Review)
Review
Under the exposure of lipids to reactive oxygen species (ROS), lipid peroxidation proceeds non-enzymatically and generates an extremely heterogeneous mixture of reactive carbonyl species (RCS). Among them, HNE, HHE, MDA, methylglyoxal, glyoxal, and acrolein are the most studied and/or abundant ones. Over the last decades, significant progress has been achieved in understanding mechanisms of RCS generation, protein/DNA adduct formation, and their identification and quantification in biological samples. In our review, we critically discuss the advancements in understanding the roles of RCS-induced protein/DNA modifications in signaling switches to provide adaptive cell response under physiological and oxidative stress conditions. At non-toxic concentrations, RCS modify susceptible Cys residue in c-Src to activate MAPK signaling and Cys, Lys, and His residues in PTEN to cause its reversible inactivation, thereby stimulating PI3K/PKB(Akt) pathway. RCS toxic concentrations cause irreversible Cys modifications in Keap1 and IKKβ followed by stabilization of Nrf2 and activation of NF-κB, respectively, for their nuclear translocation and antioxidant gene expression. Dysregulation of these mechanisms causes diseases including cancer. Alterations in RCS, RCS detoxifying enzymes, RCS-modified protein/DNA adducts, and signaling pathways have been implicated in various cancer types.
Topics: Humans; Lipid Peroxidation; DNA Adducts; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Reactive Oxygen Species; Neoplasms
PubMed: 37939506
DOI: 10.1016/j.bbrc.2023.149167 -
Biochemical and Biophysical Research... Jul 2023Acute kidney injury is an important global health concern as it is associated with high morbidity and mortality. Polyamines, essential for cell growth and proliferation,...
Acute kidney injury is an important global health concern as it is associated with high morbidity and mortality. Polyamines, essential for cell growth and proliferation, are known to inhibit cardiovascular disease. However, under conditions of cellular damage, toxic acrolein is produced from polyamines by the enzyme spermine oxidase (SMOX). We used a mouse renal ischemia-reperfusion model and human proximal tubule cells (HK-2) to investigate whether acrolein exacerbates acute kidney injury by renal tubular cell death. Acrolein visualized by acroleinRED was increased in ischemia-reperfusion kidneys, particularly in tubular cells. When HK-2 cells were cultured under 1% oxygen for 24 h, then switched to 21% oxygen for 24 h (hypoxia-reoxygenation), acrolein accumulated and SMOX mRNA and protein levels were increased. Acrolein induced cell death and fibrosis-related TGFB1 mRNA in HK-2 cells. Administration of the acrolein scavenger cysteamine suppressed the acrolein-induced upregulation of TGFB1 mRNA. Cysteamine also inhibited a decrease in the mitochondrial membrane potential observed by MitoTrackerCMXRos, and cell death induced by hypoxia-reoxygenation. The siRNA-mediated knockdown of SMOX also suppressed hypoxia-reoxygenation-induced acrolein accumulation and cell death. Our study suggests that acrolein exacerbates acute kidney injury by promoting tubular cell death during ischemia-reperfusion injury. Treatment to control the accumulation of acrolein might be an effective therapeutic option for renal ischemia-reperfusion injury.
Topics: Mice; Animals; Humans; Acrolein; Cysteamine; Kidney; Acute Kidney Injury; Cell Death; Reperfusion Injury; Ischemia; Polyamines; Oxygen; Disease Models, Animal; Hypoxia; RNA, Messenger
PubMed: 37187091
DOI: 10.1016/j.bbrc.2023.05.029