Tobacco Smoke is a Source of Toxic Reactive Glycation Products (original) (raw)
Related papers
Molecular Medicine, 1998
Background: Advanced glycation endproducts (AGEs) arise from the spontaneous reaction of reducing sugars with the amino groups of macromolecules. AGEs accumulate in tissue as a consequence of diabetes and aging and have been causally implicated in the pathogenesis of several of the end-organ complications of diabetes and aging, induding cataract, atherosderosis, and renal insufficiency. It has been recently proposed that components in mainstream cigarette smoke can react with plasma and extracellular matrix proteins to form covalent adducts with many of the properties of AGEs. We wished to ascertain whether AGEs or immunochemically related molecules are present at higher levels in the tissues of smokers. Materials and Methods: Lens and coronary artery specimens from nondiabetic smokers and nondiabetic nonsmokers were examined by immunohistochemistry, immunoelectron microscopy, and ELISA employing several distinct anti-AGE antibodies. In addition, lenticular extracts were tested for AGE-associated fluorescence by fluorescence spectroscopy.
The International journal of angiology : official publication of the International College of Angiology, Inc, 2015
The interaction of advanced glycation end products (AGEs) with its cell-bound receptor RAGE increases gene expression and release of proinflammatory cytokines and increase generation of reactive oxygen species (ROS). Circulating receptors, soluble RAGE (sRAGE), and endosecretory RAGE (esRAGE) by binding with RAGE ligands have protective effects against AGE-RAGE interaction. Cigarette smoking is a risk factor for coronary artery disease, stroke, and peripheral vascular disease. This article reviews; if the AGE-RAGE axis is involved in the cigarette smoke-induced cardiovascular diseases. There are various sources of AGEs in smokers including, gas/tar of cigarette, activation of macrophages and polymorphonuclear leukocytes, uncoupling of endothelial isoform of nitric oxide synthase (eNOS) and xanthine oxidase. The levels of AGEs are elevated in smokers. Serum levels of sRAGE have been reported to be reduced, elevated, or unchanged in smokers. Mostly the levels are reduced. There is one...
Recent Advances in the Associations of Advanced Glycation End Products (Ages) and Cancer
American Journal of Biomedical Science & Research, 2019
Mini Review Advanced glycation end products (AGEs) are a group of heterogeneous molecules formed by non-enzymatic reactions. These reactions occur between the carbonyl group of reducing sugars, such as glucose, fructose, ADP-ribose, or dicarbonyl derivatives such as glyoxal, methyl glyoxal, 3-deoxyglucosone, and the nucleophilic amino group of proteins, lipids or nucleic acids [1,2]. Advanced glycation end products are generated exogenously in food, especially in thermal processed food, but are also produced endogenously under physiological or pathological conditions [1,3,4]. In vivo glycation takes place slowly but continuously throughout life. The accumulation of AGEs has been linked to agerelated diseases including diabetes mellitus, atherosclerosis and cancer [5,6,7]. Advanced glycation end products can be divided into fluorescent and nonfluorescent forms, as well as cross-and non-cross-linked types. The commonest AGEs are 3-deoxyglucosone-derived pyrraline and pentosidine, glyoxal-or methyl glyoxal-derived Nε-(carboxylmethyl)-L-lysine (CML), the cross-linked glyoxal-lysine dimer (GOLD), and methylglyoxal-lysine dimer (MOLD) and S-carboxymethylcysteine. It has been shown that the levels of these compounds are high in plasma and tissues during aging as well as in various cancers [8,9]. The underlying mechanisms of AGE formation include the Maillard reaction, the polyol and glycolysis pathways, lipid peroxidation, and high oxidative stress, almost all of which require a hyper glycemic cellular microenvironment. Cancer cells are characterized by an increased glucose uptake and a high rate of glycolysis (the Warburg effect), to meet their energy requirements. Consequently, under hyper glycemic conditions, glycation is increased in cancer cells and AGE accumulation is accelerated. The gradual build-up of AGEs is involved in the pathogenesis and development of cancers [10,11]. Cancer patients show increased AGE levels in their tumour tissues, plasma and in their serum samples [12,13]. For example, primary colorectal carcinoma tissue displays a higher intensity of AGE expression compared with normal colonic mucosa [14]. The serum concentrations of glucose-derived AGEs in gastric cancer patients without diabetes are found to be markedly increased compared with healthy people of comparable age [15,16]. Methylglyoxal and 3-deoxyglucosone modified DNA were found in sera of breast cancer patients and various AGE modified proteins occurred in their tumor tissues [17]. The levels of AGEs are increased in the saliva of myeloma patients with bone lesions [18]. Histone proteins are particularly susceptible to glycation because of their long half-lives and the nucleophilic tails of their molecules Copy Right@ Qiuyu Wang This work is licensed under Creative Commons Attribution 4.0 License AJBSR.MS.ID.000888.
Antioxidants & Redox Signaling, 2010
Cigarette smoking is a major risk factor for developing pulmonary and cardiovascular diseases as well as some forms of cancer. Understanding the mechanisms by which smoking contributes to disease remains a major research focus. Increased levels of carbonylated serum proteins are present in smokers; albumin is the major carbonylated protein in the bronchoalveolar lavage fluid of older smokers. We have investigated the susceptibility of human serum albumin (HSA) to a,b-unsaturated aldehyde-induced carbonylation when exposed to whole-phase cigarette smoke extract (CSE). Fluorescence studies with fluorescent probes showed depletion of HSA Cys34 free thiol and marked decrease of free Lys residues. Spectrophotometric and immunochemical carbonyl assays after carbonyl derivatization with 2,4-dinitrophenylhydrazine revealed the formation of covalent carbonyl adducts. Nanoscale capillary liquid chromatography and electrospray tandem mass spectrometry analysis detected acrolein and crotonaldehyde Michael adducts at Cys34, Lys525, Lys351, and His39 at all the CSE concentrations tested. Lys541 and Lys545 were also found to form a Schiff base with acrolein. The carbonyl scavenger drugs, hydralazine and pyridoxamine, partially prevented CSE-induced HSA carbonylation. Carbonylation of HSA associated with cigarette smoking might result in modifications of its antioxidant properties and transport functions of both endogenous and exogenous compounds. Antioxid. Redox Signal. 12, 349-364.
Smoking and lung cancer-induced changes in N-glycosylation of blood serum proteins
Glycobiology, 2012
Glycosylation is a key post-translational protein modification which appears important in malignant transformation and tumor metastasis. Abnormal glycosylation of different proteins can often be measured in the blood serum. In this study, we extend our serum-based structural investigations to samples provided by patients diagnosed with lung cancer, paying particular attention to the effects of smoking on the serum glycomic traces. Following a battery of glycomic tests, we find that several fucosylated tetra-antennary structures with varying degrees of sialylation are increased in their abundances in control samples provided by the former smokers, with further elevations in the lung cancer patients who were former smokers. Further detailed investigations demonstrated that the level of outer-arm fucosylation was elevated in the control samples of the former smokers and again in the lung cancer samples provided by the former smokers. This trend was particularly noticeable for the tri-and tetra-antennary structures. Different ratios of sialylation linkages were also observed that could be correlated with the different states of health and smoking status. Decreases in the abundance levels of isomers with two and three α2,3-linked sialic acids and an increased abundance of an isomer with two α2,6-linked sialic acids were noted for a fucosylated tri-sialylated tri-antennary glycan. These results demonstrate the long-term effects of smoking on glycomic profiles and that this factor needs to be considered in these and other serum-based analyses.
Involvement of Various Molecular Events in Cellular Injury Induced by Smokeless Tobacco
Chemical Research in Toxicology, 2010
Smokeless tobacco (ST) consumption is implicated in the pathogenesis of oral diseases, including cancer. However, its pathological effect in other organs is not well understood. In the present study, the effect of aqueous extract of smokeless tobacco (AEST) prepared from "gutkha" (a form of ST) on the xenobiotic drug-metabolizing enzymes, histopathological changes, and damage to the genetic material in lung, liver, and kidney of rats was evaluated. Animals were orally administered AEST at a low dose (L-AEST, 96 mg/kg body wt/day) for 2 (L-AEST 2 ) and 28 weeks (L-AEST 28 ) and at a high dose (H-AEST, 960 mg/kg body wt/day) for 2 weeks (H-AEST 2 ). Real-time PCR and immunohistological studies showed that administration of L-AEST 2 did not induce the expression of phase I cytochrome P450s (CYP1A1, 1A2, and 2E1) and phase II µ-glutathione-s-transferase (GST-µ) drug-metabolizing enzymes in lung, liver, and kidney. Although H-AEST 2 administration significantly induced both gene and protein expression of CYP1A1, 1A2, and 2E1 in all of the above organs, it mildly expressed the phase II detoxifying enzyme, GST-µ, in type I and type II epithelial cells of lung and in proximal tubular cells of kidney. L-AEST 28 enhanced the gene and protein expression of CYP1A1, 1A2, and 2E1 in lung, liver, and kidney in a differential manner and induced the expression of GST-µ in lung and kidney. L-AEST 28 induced the micronuclei formation in the peripheral blood mononuclear cells, TNF-R in plasma, and myeloperoxidase activity in the organs. L-AEST 28 significantly enhanced Bax, p53, and NF-κB and decreased Bcl-2 gene expressions differentially in an organ-specific manner. The differential changes in these organs due to AEST might be due to their different physiological functions and variable sensitivities toward the metabolites of AEST, which create a microenvironment favorable for AEST-induced pathogenesis. This study broadens the insight into the different molecular mechanisms in various organs, which appear to be deregulated due to AEST. Understanding these processes may help in clinical treatment planning strategies for tobacco-related diseases.
Archives of Biochemistry and Biophysics, 1998
forefront of the social debate pitting smokers against Environmental tobacco smoke (ETS) is a hotly debated nonsmokers. While the risks associated with smoking social, political, and scientific issue, pitting smokers' have been fairly well documented, the risks from ETS rights against the health and safety of nonsmokers. Strikare not as well known or accepted. Environmental toing an acceptable balance between the two depends bacco smoke consists of exhaled tobacco smoke and largely on the potential health hazard assessment of ETS. side-stream smoke (SSS) which contains many free Studies from this laboratory have shown that exposure radicals and redox-active compounds (1). SSS is that to side-stream cigarette smoke (SSS), the major composmoke produced from the lit end of a burning cigarette. nent of ETS, significantly increases oxidative stress in Our study used SSS, since up to 85% of indoor air pollumouse heart, liver, and lung tissues. This study measures tion by tobacco smoke by-products is caused by SSS (2). the level of oxidative damage to mouse liver, lung, and It is known that SSS is unfiltered and generated from heart DNA as a result of this oxidative stress. Adult fetobacco combustion at a lower temperature than mainmale Balb/c mice were exposed to a regimen consisting stream cigarette smoke. These differences create a of sequences of a 30-min exposure followed by a 90-min smoke whose composition is chemically different from nonexposure. This regimen was performed once for the mainstream cigarette smoke and which is more toxic single exposure and repeated three times for the triple on an equal molar basis (2).
Archives of Toxicology
Aging and smoking are major risk factors for cardiovascular diseases (CVD). Our in vitro study compared, in the context of aging, the effects of the aerosol of Tobacco Heating System 2.2 (THS; an electrically heated tobacco product) and 3R4F reference cigarette smoke (CS) on processes that contribute to vascular pathomechanisms leading to CVD. Young and old human aortic smooth muscle cells (HAoSMC) were exposed to various concentrations of aqueous extracts (AE) from 3R4F CS [0.014–0.22 puffs/mL] or THS aerosol [0.11–1.76 puffs/mL] for 24 h. Key markers were measured by high-content imaging, transcriptomics profiling and multianalyte profiling. In our study, in vitro aging increased senescence, DNA damage, and inflammation and decreased proliferation in the HAoSMCs. At higher concentrations of 3R4F AE, young HAoSMCs behaved similarly to aged cells, while old HAoSMCs showed additional DNA damage and apoptosis effects. At 3R4F AE concentrations with the maximum effect, the THS AE showe...
International journal of experimental pathology, 1994
The possible role of reactive oxygen species in the toxicity of smokeless tobacco (ST) was explored. The effects of an aqueous smokeless tobacco extract (STE) at doses of 125, 250 and 500 mg STE/kg in rats on the induction of hepatic mitochondrial and microsomal lipid peroxidation and the incidence of hepatic nuclear DNA damage 24 hours post treatment were examined. Dose-dependent increases of 1.8, 2.3 and 4.4-fold in mitochondrial and 1.5, 2.1 and 3.6-fold in microsomal lipid peroxidation occurred at 125, 250 and 500 mg STE/kg, respectively, relative to control values. At these same three doses of STE, 1.3, 1.4 and 2.7-fold increases in hepatic DNA single-strand breaks occurred relative to control values. STE administration also resulted in significant increases in excretion of urinary metabolites. Urinary excretion of the four lipid metabolites malondialdehyde (MDA), formaldehyde (FA), acetaldehyde (ACT) and acetone (ACON) was monitored by HPLC for 72 hours after treatment of rats...