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At least 19 recordsLinked to original sources
PubMed2006

Oligomer formation in evaporating aqueous glyoxal and methyl glyoxal solutions.

Glyoxal and methyl glyoxal are common secondary atmospheric pollutants, formed from aromatic and terpene precursors. Both compounds are extremely water-soluble due to dihydrate formation and partition into cloudwater. In this work, FTIR-ATR and mass measurements indicate that both compounds remain primarily in the condensed phase due to oligomer formation when aqueous solution droplets are evaporated, regardless of concentration (> or = 1 mM) or, for glyoxal, droplet evaporation rate. FTIR spectral analyses suggestthat oligomer formation is triggered by conversion from dihydrate to monohydrate forms, which are still nonvolatile but contain reactive carbonyl groups. Methyl glyoxal hemiacetal formation is observed by changes in the C-0/C=0 stretch peak area ratio. The formation of glyoxal oligomers is detected by a dramatic shift of the C-0 stretching peak toward low frequencies. Glyoxal oligomer peaks at 1070 cm(-1), 950 cm(-1), and 980 cm(-1) are assigned to free C-OH stretch, dioxolane-linked C-OC asymmetric stretch, and tentativelyto non-dioxolane-linked C-OC stretches, respectively. Acids have little effect on glyoxal oligomer formation; however, base interrupts oligomer formation by catalyzing glyoxal hydration and disproportionation to glycolic acid. Since glyoxal and methyl glyoxal are commonly found in cloudwater and are expected to remain largely in the aerosol phase when cloud droplets evaporate, this process may be a source of secondary organic aerosol by cloud processing.

Glyoxal↗
PubMed2002

Alteration of the intracellular pH and apoptosis induction in a retinal cell line by the AGE-inducing agent glyoxal.

BACKGROUND: Methylglyoxal and glyoxal, intermediate products of glycation, are known to accelerate glycation and the formation of advanced glycation endproducts (AGEs). These mechanisms may play a role in the degenerative progression of diabetic retinopathy and macular degeneration. The present study was undertaken to elucidate the retinal neurotoxicity of the Maillard reaction intermediate alpha-oxoaldehyde glyoxal. METHODS: E1A-NR3 is an immortalized retinal cell line that manifests specific phenotypes of retinal neurons. These cells were incubated with 0 microM (control), 200 microM, 400 microM, and 800 microM glyoxal for different lengths of time. For intracellular pH measurements, cells were incubated for 30 min with BCECF-AM prior to measurement of the emission ratio at two wavelengths. For semiquantitative analysis of the mitochondrial potential, cells were incubated for 15 min with 5,5',6,6'-tetrachloro-1,1', 3,3'-tetraethylbenzimidazolylcarbocyanine iodide (JC-1). For detection of apoptotic cells, cultures were incubated for 15 min with YO-PRO-1 iodide. Immunohistochemical labeling of cell components, which are indicative for apoptosis like active caspase-3 and the caspase cleavage product fractin, was performed after fixation. DNA gel electrophoresis was carried out to detect apoptotic cell death at the DNA level. RESULTS: Morphological changes in living cells after glyoxal incubation showed signs of cell damage, including cell membrane blebbing and aggregation of intracellular organelles. Glyoxal produced a dose- and time-dependent acidification from physiological pH to pH 7.2. The semiquantitative analysis of mitochondrial membrane potential in living control cells showed nearly all mitochondria with intact hyperpolarized membranes. One hour after the beginning of incubation with 200 microM glyoxal we found most mitochondria depolarized but still with an elongated shape and only regional swelling. With higher glyoxal concentrations more depolarized mitochondria developed blebs and were located around the nucleus. The membrane permeability assay with the nucleic acid stain YO-PRO-1 showed increasing cell membrane permeability with time and glyoxal dose and, finally, nuclear fragmentation. By means of immunohistochemistry we found a glyoxal-induced accumulation of the AGE N(epsilon)-(carboxymethyl) lysine in the cytoplasm and nuclei. The cells were immunoreactive for active caspase-3 after glyoxal in a dose-dependent manner. Neurofilament protein was strongly expressed in controls and disappeared gradually with increasing glyoxal concentration. The immunoreactivity for the caspase cleavage product fractin was found in most of the cells after 800 microM glyoxal. DNA gel electrophoresis showed DNA ladder formation. CONCLUSIONS: The ability of glyoxal to induce apoptosis was confirmed by our findings demonstrating the time- and dose-dependent acidification of retinal cells. The onset of acidification is a hallmark because acidification is a measurable cytosolic event that follows the mitochondrial change but precedes caspase activation. Therefore, monitoring of pHi can allow one to assess cell stresses such as hypoxia, and metabolic stress (AGEs), and to test whether these stresses have a cumulative effect on apoptosis induction. Our study showed that intracellular pH and mitochondrial potential in living retinal cells are useful parameters for monitoring metabolic status in retinal tissue. These findings may be relevant in the study of retinal cell death mechanisms associated with age-related diabetic retinopathy and macular degeneration.

Animals↗
PubMed1989

Effect of glyoxal pretreatment on radiation-induced genetic damage in Drosophila melanogaster.

The effects of glyoxal and of glyoxal pretreatments on radiation-induced genetic damage were investigated in Drosophila melanogaster mature sperm, by means of sex-linked recessive and dominant lethality, reciprocal translocation and chromosome loss tests. In addition, the possible mutagenic effect of glyoxal was assessed in postmeiotic cells up to 7 days after treatment. The results obtained show: (1) the frequencies of recessive lethals after glyoxal treatment were within control values, (2) no clastogenic effect of glyoxal was observed, (3) glyoxal pretreatment did not modify the frequency of recessive lethals induced by X-rays, (4) after pretreatment with glyoxal a consistent, though not significant, increase was seen in the frequency of reciprocal translocations in 3 replicate experiments, (5) the yield of dominant lethals and of complete and partial chromosome loss induced by radiation was significantly increased by pretreatments with glyoxal. It is suggested that the increase of the frequency of genetic endpoints resulting from chromosome breakage, when glyoxal was administered prior to irradiation, could be ascribed to: (a) a sensitizing action of glyoxal to the clastogenic effect of ionizing radiation; (b) the formation of reactive species by the interaction of glyoxal with radiation; and/or (c) interference of glyoxal with the normal handling of radiation-induced lesions in mature postmeiotic male cells.

Aldehydes↗
PubMed2004

The cytotoxic mechanism of glyoxal involves oxidative stress.

Glyoxal is a reactive alpha-oxoaldehyde that is a physiological metabolite formed by lipid peroxidation, ascorbate autoxidation, oxidative degradation of glucose and degradation of glycated proteins. Glyoxal is capable of inducing cellular damage, like methylglyoxal (MG), but may also accelerate the rate of glycation leading to the formation of advanced glycation end-products (AGEs). However, the mechanism of glyoxal cytotoxicity has not been precisely defined. In this study we have focused on the cytotoxic effects of glyoxal and its ability to overcome cellular resistance to oxidative stress. Isolated rat hepatocytes were incubated with different concentrations of glyoxal. Glyoxal by itself was cytotoxic at 5mM, depleted GSH, formed reactive oxygen species (ROS) and collapsed the mitochondrial membrane potential. Glyoxal also induced lipid peroxidation and formaldehyde formation. Glycolytic substrates, e.g. fructose, sorbitol and xylitol inhibited glyoxal-induced cytotoxicity and prevented the decrease in mitochondrial membrane potential suggesting that mitochondrial toxicity contributed to the cytotoxic mechanism. Glyoxal cytotoxicity was prevented by the glyoxal traps d-penicillamine or aminoguanidine or ROS scavengers were also cytoprotective even when added some time after glyoxal suggesting that oxidative stress contributed to the glyoxal cytotoxic mechanism.

Animals↗
PubMed2001

Formation of the 1,N2-glyoxal adduct of deoxyguanosine by phosphoglycolaldehyde, a product of 3'-deoxyribose oxidation in DNA.

Oxidation of deoxyribose in DNA results in the formation of a variety of electrophilic products that have the potential to react with nucleobases to form adducts. We now report that 2-phosphoglycolaldehyde, a model for the 3'-phosphoglycolaldehyde residue generated by 3'-oxidation of deoxyribose in DNA, reacts with dG and DNA to form the diastereomeric 1,N2-glyoxal adducts of dG, 3-(2-deoxy-beta-D-erythro-pentofuransyl)-6,7-dihydro-6,7-dihydroxyimidazo[1,2-a]purine-9(3H)-one. The glyoxal adducts were the predominant species formed under biological conditions (pH 7.4 and 37 degrees C), with several minor fluorescent adducts, including 1,N6-ethenoadenine. The adducts were fully characterized by HPLC, mass spectrometry, and UV and NMR spectroscopy. The reaction of 2-phosphoglycolaldehyde with dG occurred with a rate constant of 10(-6) M(-1) s(-1) compared to the rate constants of 0.08 and approximately 10(-9) M(-1) s(-1) for the reactions of glyoxal and glycolaldehyde with dG, respectively. The kinetic results rule out contamination of 2-phosphoglycolaldehyde preparations with glyoxal as the basis for our observations. The rate constant for the formation of glyoxal from 2-phosphoglycolaldehyde (10(-8) s(-1)) is consistent with glyoxal generation being the rate-limiting step in the formation of dG adducts in reactions with 2-phosphoglycolaldehyde. Mechanistic studies were also undertaken to define the basis for the different oxidation states of glyoxal and 2-phosphoglycolaldehyde. Although 2-phosphoglycolaldehyde produced a weak ESR signal consistent with generation of hydroxyl radicals and it caused DNA strand breaks at high concentrations, the formation of the glyoxal adducts of dG was insensitive to radical quenchers (e.g., sorbitol) and independent of molecular oxygen. In contrast, the formation of glyoxal-dG adducts with glycolaldehyde was dependent on molecular oxygen and quenched by sorbitol, and the glycolaldehyde-glyoxal rearrangement produced a strong ESR signal characteristic of alkyl radicals. These observations are consistent with a model in which glyoxal is generated from 2-phosphoglycolaldehyde by a nonradical, oxygen-independent mechanism that is currently under investigation. Our results provide a mechanistic basis for the observation by Murata-Kamiya et al. [(1995) Carcinogenesis 16, 2251-2253] that oxidation of DNA with the Fe(II)-EDTA complex results in the formation of the glyoxal adducts of dG.

Aldehydes↗
PubMed2005

Occupational contact allergy to glyoxal.

Glyoxal is a dialdehyde that is used as a disinfectant in health care and dentistry work. Allergic contact dermatitis from glyoxal has been described in these occupations. We analysed our patient data from 1998 to 2004 for allergic reactions to glyoxal. 20 patients had allergic reactions to glyoxal on patch testing. 5 of these patients worked in dentistry and 4 of them had present exposure to glyoxal. 9 patients were machinists without obvious exposure to glyoxal. A grinder with work-related facial dermatitis is described in detail. The chemical analysis of air samples from his workplace revealed 9.4-21 microg/m3 glyoxal. Glyoxal was also present in the used metal-working fluid, and apparently it had been formed during grinding. The remaining 6 patients worked in miscellaneous occupations and had no present exposure to glyoxal. Glyoxal is irritant on patch testing. Especially, solitary reactions to glyoxal 10% in aq. may be false-positive irritant reactions. 9 (45%) of our patients reacted to formaldehyde or glutaraldehyde. Glyoxal is an important allergen in dentistry and medical care, and we recommend it to be added to the antimicrobial patch test series. It also seems to be a 'hidden' allergen in the metal industry.

Adult↗
PubMed1998

DNA modifications by the mutagen glyoxal: adduction to G and C, deamination of C and GC and GA cross-linking.

The mutagen glyoxal was reacted with DNA or deoxynucleosides under physiological conditions (pH 7.4, 37 degrees C) in vitro and the products were analyzed by HPLC coupled with a photodiode array UV detector. The efficient formation of a cyclic glyoxal-dG adduct (dG+) was observed in DNA, as well as with dG. The monomeric dG + was gradually decomposed to dG at pH 7.4 and 37 degrees C (t1/2 14.8 h). However, the dG+ formed in single- and double-stranded DNA was rather stable under physiological conditions and the half-lives were 19 and 40 times longer respectively than that of the monomer (t1/2 285 and 595 h respectively). By reaction of glyoxal with deoxycytidine (dC), the deamination products deoxyuridine and 5-hydroxyacetyl-dC (dC+) were formed. Under the same conditions, 5-methyl-dC was deaminated to dT at a higher rate. Deoxyuridine was also formed in DNA by glyoxal treatment. When glyoxal was reacted with various combinations of deoxynucleosides for a prolonged period, dG-glyoxal-dC (GgC), dG-glyoxal-dA (GgA), dG-glyoxal-dG (GgG) and dC-glyoxal-dC (CgC) cross-links were detected, although structures were not assigned unequivocally. Among these, the former two, the GC and GA cross-links, were detected in glyoxal-treated DNA. The yields of these products in DNA were in the following order; dG+ > dU > GgA > GgC > dC+. These DNA modifications may be relevant to glyoxal-induced mutations at GC pairs.

Cytosine↗
PubMed1991

Characteristics of mutagenesis by glyoxal in Salmonella typhimurium: contribution of singlet oxygen.

The characteristics of mutagenesis by glyoxal in Salmonella tester strains TA100 and TA104, and particularly a possible role of active oxygen species, were investigated. Glyoxal was converted into a non-mutagenic chemical with glutathione (GSH) by glyoxalase I, and the mutagenic activity was enhanced by the depletion of intracellular GSH. Glyoxal caused the reduction of nitro blue tetrazolium, which was suppressed by the addition of 2,5-diphenylfuran, superoxide dismutase (SOD) and catalase (CAT), scavengers of singlet oxygen (1O2), superoxide radical (O2-) and hydrogen peroxide (H2O2), respectively. However, only the 1O2 scavenger almost completely suppressed the mutagenic activity of glyoxal. Mutagenicity assays using strains pretreated with N,N-diethyldithiocarbamate of a SOD inhibitor and strains with low levels of SOD and CAT indicated that the mutagenesis by glyoxal was independent of intracellular levels of SOD and CAT, though glyoxal itself repressed them. Therefore, all the results suggest that 1O2 formed from glyoxal is related to its mutagenesis, but that neither O2- nor H2O2 is intracellularly predominantly related to it. The action of glyoxal against SOD and CAT, and the formation of glyoxal adducts with amino acids as their components are also discussed.

Amino Acids↗
PubMed2005

Secondary organic aerosol formation by glyoxal hydration and oligomer formation: humidity effects and equilibrium shifts during analysis.

Glyoxal is a significant atmospheric aldehyde formed from both anthropogenic aromatic compounds and biogenic isoprene emissions. The chemical behavior of glyoxal relevant to secondary organic aerosol (SOA) formation and analysis is examined in GC-MS, electrospray ionization (ESI)-MS, and particle chamber experiments. Glyoxal oligomers are shown to rapidly decompose to glyoxal in GC injection ports at temperatures > or = 120 degrees C. Glyoxal dihydrate monomer is dehydrated at temperatures > or = 140 degrees C during GC analysis but shows only oligomers (n < or = 7) upon ESI-MS analysis. Thus both of these analytical techniques will cause artifacts in speciation of glyoxal in SOA. In particle chamber experiments, glyoxal (at -0.1 Torr) condensed via particle-phase reactions when relative humidity levels exceeded a threshold of -26%. Both the threshold humidity and particle growth rates (-0.1 nm/min) are consistent with a recent study performed at glyoxal concentrations 4 orders of magnitude below those used here. This consistency suggests a mechanism where the surface water layer of solid-phase aerosol becomes saturated with glyoxal dihydrate monomer, triggering polymerization and the establishment of an organic phase.

Aerosols↗
PubMed2007

13C and 1H NMR studies of ionizations and hydrogen bonding in chymotrypsin-glyoxal inhibitor complexes.

Benzyloxycarbonyl (Z)-Ala-Pro-Phe-glyoxal and Z-Ala-Ala-Phe-glyoxal have both been shown to be inhibitors of alpha-chymotrypsin with minimal Ki values of 19 and 344 nM, respectively, at neutral pH. These Ki values increased at low and high pH with pKa values of approximately 4.0 and approximately 10.5, respectively. By using surface plasmon resonance, we show that the apparent association rate constant for Z-Ala-Pro-Phe-glyoxal is much lower than the value expected for a diffusion-controlled reaction. 13C NMR has been used to show that at low pH the glyoxal keto carbon is sp3-hybridized with a chemical shift of approximately 100.7 ppm and that the aldehyde carbon is hydrated with a chemical shift of approximately 91.6 ppm. The signal at approximately 100.7 ppm is assigned to the hemiketal formed between the hydroxy group of serine 195 and the keto carbon of the glyoxal. In a slow exchange process controlled by a pKa of approximately 4.5, the aldehyde carbon dehydrates to give a signal at approximately 205.5 ppm and the hemiketal forms an oxyanion at approximately 107.0 ppm. At higher pH, the re-hydration of the glyoxal aldehyde carbon leads to the signal at 107 ppm being replaced by a signal at 104 ppm (pKa approximately 9.2). On binding either Z-Ala-Pro-Phe-glyoxal or Z-Ala-Ala-Phe-glyoxal to alpha-chymotrypsin at 4 and 25 degrees C, 1H NMR is used to show that the binding of these glyoxal inhibitors raises the pKa value of the imidazolium ion of histidine 57 to a value of >11 at both 4 and 25 degrees C. We discuss the mechanistic significance of these results, and we propose that it is ligand binding that raises the pKa value of the imidazolium ring of histidine 57 allowing it to enhance the nucleophilicity of the hydroxy group of the active site serine 195 and lower the pKa value of the oxyanion forming a zwitterionic tetrahedral intermediate during catalysis.

Animals↗
PubMed2003

Graded sensitiveness of the various retinal neuron populations on the glyoxal-mediated formation of advanced glycation end products and ways of protection.

BACKGROUND: The accumulation of advanced glycation end products (AGEs) in retinal cells is known to be associated with the risk of diabetic retinopathy. To develop a model of AGE-related metabolic stress in retinal organ cultures, we investigated the accumulation of a typical glycoxidation product (N(epsilon)-[carboxymethyl] lysine [CML]) and its possible pro-apoptotic effects on different retinal cell populations. METHODS: Retinal organ cultures (rat) were kept for 9 h in the Ames medium containing 0 (control), 5, 25, 50, 150, 300 and 800 micro M glyoxal. The expression of bax, active caspase-3, and the accumulation of CML were studied by using immunohistochemistry after the paraffin embedding of retinal explants. Apoptosis was studied using the terminal deoxynucleotidyl transferase-mediated dUTP digoxigenin nick end labeling (TUNEL) test and electron microscopy. Alpha lipoic acid (alpha-LA), sodium metavanadate (NaVO(3)), N-acetylcysteine (NAC), aminoguanidine (AG), and nicotinamide (NA) were used to influence glyoxal effects in organ cultures. RESULTS: In cultured normal non-diabetic retinae, small amounts of CML and the apoptosis-promoting factors bax and active caspase-3 were present. CML, bax and active caspase-3 increased after incubation with glyoxal. Incubation with glyoxal (<300 micro M, 9 h) increased apoptotic events in all layers. At low glyoxal concentrations, we found a graded sensitiveness of the different layers: at 25 micro M 39.4% in GCL, 28.2% in INL, 11.9% in ONL. After 800 micro M glyoxal, approximately 50% of the cells in all layers of the retina were apoptotic. In the ONL, this ratio was reduced by NaVO(3) (17%), by AG (27%), by NA (24.8%), by NAC (25.2%), and by alpha-LA (33.5%). In the INL, AG (25.9%) produced the best result. In the GCL, NAC, NaVO(3) and AG reduced apoptosis. A-LA had no significant protective effect. CONCLUSION: The glyoxal-induced rapid formation of CML shows the ability of our retina model to simulate AGE-related effects in vitro. The dose-dependent expression of apoptosis-promotor molecules indicates that the apoptosis-inducing machinery starts in most retinal cells within 9 h. The neurotoxicity of glyoxal-induced AGE formation was shown by the significantly increased rate of cell death in the retina. The significant decrease of apoptotic events (P<0.01) indicates that antioxidants and AGE formation blocker can exert a differentiated cytoprotection for each of the retinal cell layers.

Acetylcysteine↗
PubMed2005

Reaction of glyoxal with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, cytidine, thymidine, and calf thymus DNA: identification of DNA adducts.

Glyoxal (ethanedial) is an increasingly used industrial chemical that has been found to be mutagenic in bacteria and mammalian cells. In this study, the reactions of glyoxal with 2'-deoxyguanosine, 2'-deoxyadenosine, 2'-deoxycytidine, cytidine, thymidine, and calf thymus DNA have been studied in aqueous buffered solutions. The nucleoside adducts were isolated by reversed-phase liquid chromatography and characterized by their UV absorbance and 1H and 13C NMR spectroscopic and mass spectrometric features. The reaction with 2'-deoxyguanosine gave one adduct, the previously known 3-(2'-deoxy-beta-D-erythro-pentofuranosyl)-5,6,7-trihydro-6,7-dihydroxyimidazo[1,2-a]purine-9-one adduct. The reaction of 2'-deoxyadenosine with glyoxal resulted in the formation of a previously not reported N6-(hydroxyacetyl)-2'-deoxyadenosine adduct. In the reaction of glyoxal with 2'-deoxycytidine and cytidine at neutral conditions and 37 degrees C, 5-hydroxyacetyl pyrimidine derivatives were obtained. When the cytidine reaction was performed at pH 4.5 and 50 degrees C, the 5-hydroxyacetyl derivative of uridine was formed through deamination of cytidine-glyoxal. Adducts in the thymidine reaction could not be detected. In the reaction of glyoxal with calf thymus DNA, the 2'-deoxyguanosine-glyoxal and 2'-deoxyadenosine-glyoxal adducts were obtained, the former being the major adduct.

Cytidine↗
PubMed2003

Novel monoclonal antibody recognition of oxidative DNA damage adduct, deoxycytidine-glyoxal.

Glyoxal, a reactive aldehyde, is a decomposition product of lipid hydroperoxides, oxidative deoxyribose breakdown, or autoxidation of sugars, such as glucose. It readily forms DNA adducts, generating potential carcinogens such as glyoxalated deoxycytidine (gdC). A major drawback in assessing gdC formation in cellular DNA has been methodologic sensitivity. We have developed an mAb that specifically recognizes gdC. Balb/c mice were immunized with DNA, oxidatively modified by UVC/hydrogen peroxide in the presence of endogenous metal ions. Although UVC is not normally considered an oxidizing agent, a UVC/hydrogen peroxide combination may lead to glyoxalated bases arising from hydroxyl radical damage to deoxyribose. This damaging system was used to induce numerous oxidative lesions including glyoxal DNA modifications, from which resulted a number of clones. Clone F3/9/H2/G5 showed increased reactivity toward glyoxal-modified DNA greater than that of the immunizing antigen. ELISA unequivocally showed Ab recognition toward gdC, which was confirmed by gas chromatography-mass spectrometry of the derivatized adduct after formic acid hydrolysis to the modified base. Binding of Ab F3/9 with glyoxalated and untreated oligomers containing deoxycytidine, deoxyguanosine, thymidine, and deoxyadenosine assessed by ELISA produced significant recognition (p > 0.0001) of glyoxal-modified deoxycytidine greater than that of untreated oligomer. Additionally, inhibition ELISA studies using the glyoxalated and native deoxycytidine oligomer showed increased recognition for gdC with more than a 5-fold difference in IC(50) values. DNA modified with increasing levels of iron (II)/EDTA produced a dose-dependent increase in Ab F3/9 binding. This was reduced in the presence of catalase or aminoguanidine. We have validated the potential of gdC as a marker of oxidative DNA damage and showed negligible cross-reactivity with 8-oxo-2'-deoxyguanosine or malondialdehyde-modified DNA as well as its utility in immunocytochemistry. Formation of the gdC adduct may involve intermediate structures; however, our results strongly suggest Ab F3/9 has major specificity for the predominant product, 5-hydroxyacetyl-dC.

Animals↗
PubMed2005

Glyoxal inactivates glutamate transporter-1 in cultured rat astrocytes.

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by progressive motor paralysis and selective motor neuron death. There is increasing evidence that motor neuron death in ALS is mediated by glutamate toxicity resulting from reduced activity of astrocytic glutamate transporter-1 (GLT-1). Recent morphological studies have shown that Nepsilon-(carboxymethyl)lysine (CML) accumulates in reactive astrocytes of ALS spinal cords. CML is a product of post-translational protein modification by glyoxal, a reactive aldehydic intermediate. In considering these documents, it is important to determine whether GLT-1 protein modification by glyoxal might cause reduced GLT-1 activity. To address this issue, we investigated the effects of glyoxal on GLT-1 properties in cultured rat astrocytes. High performance liquid chromatography showed reduced glutamate uptake activity in the glyoxal-exposed cells. Immunocytochemical analysis displayed CML accumulation in the cytoplasm of astrocytes by glyoxal exposure. Immunoblots of immunoprecipitated GLT-1 disclosed GLT-1 CML adduct formation in the glyoxal-exposed cells. Our results indicate that glyoxal modifies GLT-1 to form CML and simultaneously deprives its glutamate uptake activity. Thus, these toxic effects of glyoxal on astrocytes might be implicated in motor neuron death in ALS.

Amino Acid Transport System X-AG↗