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H Esterbauer

Publications and source records attributed to H Esterbauer.

At least 19 recordsLinked to original sources
PubMed2000

The Gln27Glu polymorphism in the beta2-adrenergic receptor gene is not associated with morbid obesity in Austrian women.

OBJECTIVE: Beta-adrenergic receptors (betaARs) play an important role in the regulation of energy expenditure and lipid mobilization. A Gl-27Glu polymorphism in the beta2-adrenergic receptor (beta2AR) gene has recently been associated with several indices of obesity in a female Caucasian population, while the same polymorphism exhibited no association with obesity in another, albeit male, population. METHODS: We have therefore studied possible associations of the Gln27Glu and the Gly16Arg polymorphisms in the beta2AR with BMI, plasma leptin and UCP-1 mRNA expression in the intraperitoneal adipose tissue in a population of Caucasian women. RESULTS: The frequencies of the Gln27 and the Gly16 alleles as well as the beta2AR haplotypes were similar in our morbidly obese and lean subjects. Furthermore, no association was found between the Gln27Glu or the Gly16Arg polymorphisms and plasma leptin or adipose tissue UCP-1 gene expression in either group. CONCLUSIONS: We conclude that the two polymorphisms in the beta2AR gene studied are not a major factor contributing to obesity in our population.

Adipose Tissue↗
PubMed2000

Leptin, peroxisome proliferator-activated receptor-gamma, and CCAAT/enhancer binding protein-alpha mRNA expression in adipose tissue of humans and their relation to cardiovascular risk factors.

Obesity is a prevalent disorder that increases the risk for premature cardiovascular disease. The adipose tissue itself plays an active role in the regulation of fuel metabolism and energy homeostasis by expressing a number of regulatory genes, such as leptin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and CCAAT/enhancer binding protein-alpha (C/EBPalpha). To study the in vivo relationships among these genes and their associations with cardiovascular risk factors, plasma levels of leptin, lipids, apolipoproteins (apo), insulin, and glucose were measured in 216 obese, 165 nonobese, and 36 weight-losing postobese subjects. mRNA expression of leptin, PPARgamma, and C/EBPalpha in the extraperitoneal and intraperitoneal adipose tissue was quantified in subsets of subjects. In obese individuals, plasma leptin was associated with apoA-I (r=0.2346, P<0.001) and insulin (r=0.2125, P<0.002). Leptin and C/EBPalpha mRNA expression in extraperitoneal and intraperitoneal adipose tissue of obese patients was higher than in the respective tissues of nonobese or postobese subjects. No significant differences among the study groups were found for PPARgamma mRNA expression. Leptin, PPARgamma, and C/EBPalpha mRNA levels correlated with each other in the intraperitoneal and extraperitoneal fat of obese subjects, but multivariate analysis revealed that only C/EBPalpha was a predictor of leptin expression in extraperitoneal tissue (partial r=0.6096, P<0.001). Intraperitoneal PPARgamma expression was inversely related to fasting insulin (r=-0.2888, P<0.017) and a fasting insulin resistance index (r=-0.2814, P<0.021) in obese subjects. In postobese patients, intraperitoneal PPARgamma expression was associated with plasma HDL cholesterol (r=0.5695, P<0.018) and apoA-I (r=0.6216, P<0.008) but was inversely related to LDL cholesterol (r=-0.5101, P<0.03) and apoB (r=-0.6331, P<0.007). These findings suggest a relationship between plasma leptin and HDL metabolism as well as adipose-tissue site-dependent associations among leptin, C/EBP-alpha, and PPAR-gamma mRNA expression. Furthermore, our results suggest that C/EBP-alpha enhances leptin expression in vivo and that PPARgamma mRNA expression is inversely associated with cardiovascular risk factors.

Adipose Tissue↗
PubMed1999

Human peroxisome proliferator activated receptor gamma coactivator 1 (PPARGC1) gene: cDNA sequence, genomic organization, chromosomal localization, and tissue expression.

Brown adipose and muscle tissues can increase energy expenditure via adaptive thermogenesis, thereby protecting against obesity. Mouse peroxisome proliferator activated receptor gamma coactivator 1 (Pgc1) has been reported to enhance the expression of uncoupling protein-1, a key mediator of thermogenesis in brown adipose tissue (Puigserver et al., 1998, Cell 92, 829-839). We report here the characterization of the human PPARGC1 gene. PPARGC1 spans a genomic region of approximately 67 kb, is composed of 13 exons, and encodes a 91-kDa protein that exhibits 94% amino acid identity with the mouse ortholog. mRNA species, transcribed from the TATA-less promoter, are 6.4 and 5.3 kb in length due to utilization of two polyadenylation signals. Northern blotting revealed expression of both transcripts in heart, skeletal muscle, and kidney and to a lesser extent in liver, brain, and pancreas as well as in the perirenal adipose tissue of a pheochromocytoma patient. PPARGC1 was mapped to chromosome 4p15.1, a region that has been associated with basal insulin levels in Pima Indians. Hence, PPARGC1 expression might influence insulin sensitivity as well as energy expenditure, thereby contributing to the development and pathophysiology of human obesity.

Amino Acid Sequence↗
PubMed1999

A sensitive chemiluminescence method to measure the lipoxygenase catalyzed oxygenation of complex substrates.

Oxidative modification of low-density lipoprotein (LDL) has been implicated as a patho-physiological process in early atherogenesis and 15-lipoxygenases (15-LOX) may be involved. While studying the in vitro kinetics of the 15-LOX/LDL interaction, we found that the conventional spectrophotometric assays failed in the range of substrate saturation owing to the high optical density of concentrated LDL solutions. Therefore, we developed a much more sensitive assay system which was based on peroxide induced isoluminol enhanced chemiluminescence. With this method reliable kinetic data were obtained at LDL concentrations of up to 1 mg/ml. To validate this luminometric method the kinetic parameters of 15-LOX catalyzed oxygenation of linoleic acid (Km=3.7 microM, kcat=17 s-1) were determined and we observed a good agreement with previously published data obtained with a spectrophotometric assay. Moreover, we found that the kinetic constants of 15-LOX catalyzed LDL oxidation (Km=0.64 microM, kcat=0.15 s-1) are quite different from those of free fatty acid oxygenation and that the cholesterol esters are preferentially oxidized during 15-LOX/LDL interaction. Vitamin E depletion does not reduce the rate of LDL oxidation and analysis of the structure of the oxygenation products suggests that the majority of the products were formed via direct LOX catalyzed oxidation of LDL ester lipids. The luminometric method described here is not restricted to the measurement of LOX catalyzed LDL oxidation, but may also be used to determine kinetic constants for the oxidation of other complex substrates such as biomembranes or liposomes.

Arachidonate 15-Lipoxygenase↗
PubMed1999

Uncoupling protein-3 gene expression: reduced skeletal muscle mRNA in obese humans during pronounced weight loss.

AIMS: Uncoupling protein-3 is a member of a protein family that serves to dissipate energy in the form of heat thereby modulating energy expenditure. Alternative processing of uncoupling protein-3 transcripts results in two mRNA species that encode a large and small protein, perhaps differing in functional activity. Since obesity is associated with disrupted energy homeostasis, we measured muscle mRNA expression in morbidly obese and lean subjects. METHODS: The two uncoupling protein-3 mRNA species were quantified in muscle tissue using an RNase protection assay. Gene locus effects on mRNA expression were studied by quantitative allele-specific primer extension. RESULTS: In both obese and lean subjects, the mRNA species encoding the small protein isoform was twice as abundant as the mRNA species encoding the large protein isoform. Neither the total uncoupling protein-3 mRNA expression nor the molar abundance ratios of the two mRNA species differed between obese and lean male or female subjects. Women who had lost 37+/-22 kg of weight in response to dietary restriction and continued a hypocaloric diet displayed lower mRNA than obese (p<0.005) or lean women (p<0.05). Primer extension assays in lean and obese subjects showed similar allelic mRNA abundance in all but one subject studied. CONCLUSION: Muscle expression of the two uncoupling protein-3 mRNA species is similar in obese and lean people. In obese patients, prolonged hypocaloric diet downregulates uncoupling protein-3 mRNA expression in muscle and can thereby enhance its energy efficiency. Sequence substitutions at the gene locus may only be minor determinants of mRNA expression in muscle tissue.

Adult↗
PubMed1999

The cardiac acetylcholine-activated, inwardly rectifying K+-channel subunit GIRK1 gives rise to an inward current induced by free oxygen radicals.

Reactive oxygen species (ROS) play a crucial role in pathophysiology of the cardiovascular system. The present study was designed to analyze the redox sensitivity of G-protein-activated inward rectifier K+ (GIRK) channels, which control cardiac contractility and excitability. GIRK1 subunits were heterologously expressed in Xenopus laevis oocytes and the resulting K+ currents were measured with the two-electrode voltage clamp technique. Oxygen free radicals generated by the hypoxanthine/xanthine oxidase system led to a marked increase in the current through GIRK channels, termed superoxide-induced current (I(SO)). Furthermore, I(SO) did not depend on G-protein-dependent activation of GIRK currents by coexpressed muscarinic m2-receptors, but could also be observed when no agonist was present in the bathing solution. Niflumic acid at a concentration of 0.5 mmol/l did not abolish I(SO), whereas 100 micromol/l Ba2+ attenuated I(SO) completely. Catalase (10(6) i.u./l) failed to suppress I(SO), whereas H2O2 concentration was kept close to zero, as measured by chemiluminescence. Hence, we conclude that O2*- or a closely related species is responsible for I(SO) induction. Our results demonstrate a significant redox sensitivity of GIRK1 channels and suggest redox-activation of G-protein-activated inward rectifier K+ channels as a key mechanism in oxidative stress-associated cardiac dysfunction.

Acetylcholine↗
PubMed1999

Allele-specific differences in apolipoprotein C-III mRNA expression in human liver.

BACKGROUND: Sequence variations at the apolipoprotein (apo)C-III gene locus have been associated with increased plasma triglycerides. In particular, the S2 allele of an SstI polymorphism in the 3' untranslated region has been associated with hypertriglyceridemia in many populations. The aim of this study was to determine whether the variant S2 allele is related to increased mRNA expression in vivo. METHODS: We measured allele-specific apoC-III expression in liver biopsies of five obese subjects, using restriction isotyping and a primer extension method, both based on the SstI polymorphism. RESULTS: The expression of mRNA by the S1 and S2 alleles was similar in two patients, whereas the mRNA encoded by the S2 allele was 14%, 26%, and 29% more abundant than the wild-type mRNA in the remaining three patients. Because other polymorphisms at the apoC-III gene locus have been implicated in the S2-associated hypertriglyceridemia, we determined apoC-III haplotypes comprising promoter polymorphisms at -935, -641, -630, -625, -482, -455, as well as the SstI sites and a BbvI site, both located in the 3' untranslated region. None of these polymorphisms nor any haplotype exhibited a perfect association with allele-specific expression, but variation at the T-482C site correlated in four of five subjects with the relative allele abundance. CONCLUSION: These data provide preliminary evidence for allele-specific differences in apoC-III mRNA expression in vivo and suggest that such differences may contribute to associations of apoC-III gene polymorphisms with hypertriglyceridemia.

3' Untranslated Regions↗
PubMed1998

Copper can promote oxidation of LDL by markedly different mechanisms.

Oxidation of LDL (0.1 microM) in PBS with copper concentrations ranging from 0.03 to 10 microM, equal to 0.3-100 Cu2+/LDL, was investigated by monitoring the formation of conjugated dienes at 234 nm. With all 8 LDL samples examined, the kinetics changed strongly at submicromolar Cu2+ concentrations. Based on time-course of the formation of conjugated dienes, cholesteryl linoleate hydroxides and hydroperoxides as well as the antioxidant consumption, two oxidation types were distinguished. Type A oxidations, observed at relatively high Cu2+ concentrations of 10-100 Cu2+/ LDL, represented the conventional kinetics of LDL oxidation with an inhibition period (= lag-time) followed by a propagation phase. In contrast, type C oxidations proceeded after a negligibly short lag time followed by a distinct propagation phase. The rate of this propagation increased rapidly to 0.5 mol diene/mol LDL and then slowed down in the presence of alpha-,gamma-tocopherols and carotenoids, which were consumed faster than tocopherols. The increase in diene absorption was due to the formation of both hydroxides and hydroperoxides suggesting a high initial decomposition of hydroperoxides. At submicromolar concentrations of about 0.1 to 0.5 microM, type C and type A oxidation can be combined resulting in 4 consecutive oxidation phases, i.e. 1st inhibition and 1st propagation (belonging to type C), followed by 2nd inhibition and 2nd propagation (belonging to type A). Increasing copper concentrations lowered the 1st propagation and shortened the 2nd inhibition periods until they melted into one apparent kinetic phase. Decreasing [Cu2+] increased the 1st propagation and 2nd inhibition but lowered the 2nd propagation phase until it completely disappeared. A threshold copper concentration, denoted as Cu(lim), can be calculated as a kinetic constant based on the Cu2+-dependence for the rate of 2nd propagation. Below Cu(lim), LDL oxidation proceeds only via type C kinetics. The Cu2+-dependence of the oxidation kinetics suggests that LDL contains two different Cu2+ biding sites. Cu2+ at the low-affinity binding sites, with half-saturation at 5-50 Cu2+/LDL, initiates and accelerates the 2nd propagation by decomposing lipid hydroperoxides. Cu2+ bound to the high-affinity binding sites, with half-saturation at 0.3-2.0 Cu2+/LDL, is responsible for the 1st propagation. Arguments in favor and against this propagation being due to tocopherol mediated peroxidation (TMP) are discussed. If the lag-time concept is extended to the conjugated diene curves seen for combined oxidation profiles, then a true inhibition phase does not apply to this time interval, but instead represents the time elapsed before the onset of the 2nd propagation phase.

Adult↗
PubMed1998

Uncoupling protein-2 gene: reduced mRNA expression in intraperitoneal adipose tissue of obese humans.

The mitochondrial uncoupling protein-2 (UCP-2) is a recently discovered homologue of the brown adipose tissue-specific uncoupling protein and could be involved in the regulation of energy balance. Since obesity is associated with disturbed energy homeostasis, we tested the hypothesis that UCP-2 gene expression is deficient in this disorder. We determined, by a competitive reverse transcription-polymerase chain reaction assay, UCP-2 mRNA expression in intra- and extraperitoneal adipose tissues of 107 morbidly obese subjects and 31 lean control subjects. In both obese and non-obese subjects, UCP-2 mRNA abundance was higher in the intraperitoneal than in the extraperitoneal tissue (p < 0.05), but no association was observed between intra- and extraperitoneal expression in either group. Compared with lean control subjects, both male and female obese subjects displayed significantly lower average UCP-2 mRNA expression in the intraperitoneal adipose tissue (p < 0.006), while UCP-2 mRNA abundance in extraperitoneal adipose tissue was not different between obese and non-obese men and women. Intraperitoneal UCP-2 mRNA remained low in nine obese subjects who lost 23 +/- 12 kg of weight over a period of 10 +/- 5 months subsequent to weight reducing surgery. These data support the concept that impaired adipose tissue expression of UCP2 may play a role in the pathophysiology of obesity.

Adipose Tissue↗
PubMed1998

Treatment of the budding yeast Saccharomyces cerevisiae with the lipid peroxidation product 4-HNE provokes a temporary cell cycle arrest in G1 phase.

The effects of 4-hydroxy-2-nonenal (HNE) on the cell division cycle were investigated in the yeast Saccharomyces cerevisiae. A short treatment with HNE at a concentration in the range of the IC50 value in S. cerevisiae SP-4 cells induced a significant increase in the proportion of G0/G1 cells at the expense of S-phase cells. A similar delay in cell cycle progression upon treatment with HNE has recently been shown for HL-60 neoplastic cells. Long-term exposure in a synchronized yeast culture resulted in a pronounced dose-dependent block between G0G1- and S-phase, probably at or close to a point in the cell cycle that has been designated as "START." Incorporation of radioactively labeled precursors of macromolecules revealed that DNA synthesis was most susceptible to HNE in comparison to RNA and protein synthesis. Production of glutathione appeared to be required for the continuation of the cell cycle. HNE-treated yeast cells reentered the cell cycle when their glutathione content exceeded about twice the level of control cells. The release from the cell division cycle delay was followed by an enhanced growth to an extent that HNE-treated cells exceeded the number of control cells. These results indicate that HNE causes a biphasic modulation of cell proliferation. It was concluded that this effect was conserved during evolution from yeast to mammalian cells, emphasizing once more the usefulness of this unicellular organism as a model system for the investigation of the effects of free radical-derived products on the proliferation of eukaryotes.

Aldehydes↗
PubMed1998

Metabolism of 4-hydroxynonenal, a cytotoxic lipid peroxidation product, in thymocytes as an effective secondary antioxidative defense mechanism.

The metabolism of the aldehydic lipid peroxidation product, 4-hydroxynonenal (HNE),was studied in suspensions of mouse thymocytes. Thymocytes are characterized by low lipid peroxidation in comparison with other cell types notwithstanding their high content of arachidonic acid. In our study a very high capacity of HNE metabolism in thymocytes was observed: 27.7 nmol/mg w.w./min. That is about the same HNE degradation rate as determined in liver cells or small intestinal enterocytes, which are the cells with the by far highest capacity for the degradation of HNE and other aldehydic lipid peroxidation products in comparison with other cell types. The primary and secondary HNE metabolites in thymocytes were identified and quantified after the addition of 100 microM HNE to thymocyte suspensions: the glutathione-HNE conjugate, the hydroxynonenoic acid, the 1,4-dihydroxynonene, water, and the glutathione-dihydroxynonene conjugate. Furthermore, the HNE binding to proteins was measured. The very rapid HNE degradation in thymocytes besides the high amounts of lipophilic chain-breaking antioxidants is postulated to be an important secondary antioxidative mechanism and the main factor for the low accumulation of lipid peroxidation products in these cells.1668

Aldehydes↗
PubMed1998

Uncoupling protein-1 mRNA expression in obese human subjects: the role of sequence variations at the uncoupling protein-1 gene locus.

Uncoupling protein-1 (UCP-1) activity in brown adipose tissue increases thermogenesis, contributes to facultative energy expenditure in humans, and has been implicated in the pathogenesis of rodent obesity. To determine genetic factors controlling UCP-1 expression in humans, we measured intra- and extraperitoneal UCP-1 mRNA abundance levels by a competitive RT-PCR method and compared expression levels with common sequence variations in the beta3-adrenergic receptor gene and the distal UCP-1 gene promoter in obese human subjects. While median and average UCP-1 mRNA levels in both the intra- and extraperitoneal tissue were lower in subjects heterozygous for the Trp64Arg mutation in the beta3-adrenergic receptor gene, this difference was not statistically significant. However, a strong association of intraperitoneal UCP-1 mRNA abundance with the UCP-1 gene polymorphism at -3826 relative to the transcription start site was observed that explained 19.3% of the interindividual variability. The minor allele imparted a dose-dependent reduction on UCP gene expression. The importance of sequence variations at the UCP-1 gene locus as a common source of UCP-1 mRNA abundance variability was supported by allele-specific expression studies utilizing a newly identified polymorphism in exon 2 of the UCP-1 gene that predicts a substitution of alanine by threonine. In four subjects heterozygous for the -3826 polymorphism, the mRNA species transcribed from the wild-type allele accounted for 63+/-6% percent of total intraperitoneal mRNA abundance. In one subject homozygous for the minor promoter allele, wild-type mRNA was also more abundant than variant mRNA. Thus, the UCP-1 polymorphism at -3826 is probably only a marker for a frequent mutation causing reduced mRNA expression.

Adipose Tissue↗
PubMed1997

Risk factors for microangiopathy-related cerebral damage in the Austrian stroke prevention study.

Microangiopathy-related cerebral damage (MARCD) represents a common incidental MRI observation in the elderly. The risk factors of such findings are widely unknown. We therefore performed MRI in 349 randomly selected volunteers (ages 50 to 70 years) without neuropsychiatric disease, and evaluated the association of MARCD with conventional and recently suggested cerebrovascular risk factors such as apolipoprotein E genotypes, plasma concentrations of essential antioxidants and anticardiolipin antibody titres. MARCD was defined as evidence of early confluent and confluent deep white matter hyperintensities and lacunes. It was present in 71 (20.3%) subjects. Individuals with MARCD were older than those without such findings (62.7 years vs 59.6 years; P=0.0001). They had a higher rate of arterial hypertension (45.1% vs 28.1%; P=0.006) and cardiac disease (50.7% vs 37.1%; P=0.04), higher systolic blood pressure readings at exam (144.4 mmHg vs 136.7 mmHg; P=0.004), and higher serum fibrinogen concentrations (327.1 mg/dl vs 292.5 mg/dl; P=0.001). Their levels of total cholesterol (217.6 mg/dl vs 231.2; P=0.009), apolipoprotein A-I (167.3 mg/dl vs 177.4 mg/dl, P=0.02), lycopene (0.17 micromol/l vs 0.24 micromol/l; P=0.003), retinol (1.91 micromol/l vs 2.10 micromol/l; P=0.02) and alpha-tocopherol (27.55 micromol/l vs 31.14 micromol/l; P=0.001) were significantly lower. Forward stepwise regression analysis created a model of independent predictors of MARCD with age entering first (odds ratio 2.01/10 years), fibrinogen second (odds ratio 2.45/100 mg/dl), alpha-tocopherol third (odds ratio 0.55/10 micromol/l), and arterial hypertension fourth (odds ratio 1.96). The association of MARCD with various treatable clinical conditions may have preventive implications.

Aged↗
PubMed1997

Low and very low density lipoprotein composition and resistance to copper-induced oxidation are not notably modified in smokers.

To study whether tobacco use was associated with oxidative phenomena affecting lipoproteins, we estimated susceptibility of LDL and VLDL to an in vitro copper-mediated oxidation, and measured serum autoantibody titers against oxidized LDL in 45 middle-age healthy nonsmokers, 35 smokers and 37 ex-smokers of both sexes, taking into account the detailed lipid composition of the lipoproteins. VLDL from female smokers had higher triglyceride, phospholipid, apolipoprotein E and alpha-tocopherol content and showed a higher rate of copper-induced oxidation in comparison with those from nonsmokers (P < or = 0.05) whereas the relative composition of these particles in saturated, mono- or poly-unsaturated fatty acids was not modified by tobacco consumption. After adjustment for triglyceride content, no statistically significant difference in oxidation rate was observed. Lipid, alpha-tocopherol and protein composition of LDL did not appear to be influenced by smoking; in accordance with these observations, no difference in indices of in vitro oxidizability of LDL was noticed between the different groups. Autoantibody titers against oxLDL were similar in smokers and nonsmokers. We conclude that, in supposed healthy individuals, smoking does not seem to be associated with notable variations in composition of VLDL and LDL or with an increase of oxidizability of these atherogenic lipoproteins.

Adolescent↗
PubMed1997

Antioxidant role of melatonin in lipid peroxidation of human LDL.

The antioxidant effect of melatonin on LDL oxidation was studied in vitro using either a thermolabile initiator or copper ions to induce lipid peroxidation. Loading of LDL with melatonin showed only weak protection against oxidative damage as compared to alpha-tocopherol. In the presence of high concentrations of melatonin (1000 mol/mol LDL) in the medium a clear protective effect was found during lag- and propagation phase, albeit weaker than after loading with alpha-tocopherol. It is concluded that melatonin is not incorporated into LDL in sufficient concentrations to prevent lipid peroxidation effectively. When melatonin is present in the incubation medium during oxidation, a partitioning equilibrium between aqueous and lipid phase is established. Only under these conditions can melatonin act as a chain breaking antioxidant. The concentrations required, however, are far beyond those found in human plasma. Therefore, the data in this study do not support a direct physiological relevance of melatonin as an antioxidant in lipid peroxidation processes.

Amidines↗
PubMed1997

The interaction of lower alcohols with apoB in spin labeled human plasma low density lipoproteins (LDL).

In this study the interaction of alcohol with the macromolecular lipid-protein assembly represented by human plasma low density lipoproteins (LDL) was investigated. The spin label which covalently binds to the side chain amino group of lysines as well as terminal amino groups was attached to the spin labeled apoprotein (apoB) of native LDL in order to observe the protein component in the electron spin resonance (ESR) spectrum. The interaction of different lower alcohols (methanol, ethanol, propanol and butanol) with the spin labeled LDL was studied for two alcohol concentrations (0.3 and 3.0 M). The ESR spectra indicate a decrease of the hyperfine splitting and narrowing of the linewidth upon the action of alcohol that leads to the conclusion that alcohol provokes a change in the apoB conformation. These findings are explained by following the arguments of the phospholipid mediated mechanism of alcohol action, through the modulation of the lipid packing free volume which results in the protein conformational change.

Alcohols↗
PubMed1997

Increased stress parameter synthesis in the yeast Saccharomyces cerevisiae after treatment with 4-hydroxy-2-nonenal.

The metabolism of glutathione (GSH), a marker of oxidative stress and trehalose, a rather general physiological stress marker, was examined in exponentially growing Saccharomyces cerevisiae cells after treatment with 4-hydroxynonenal (HNE). GSH was entirely depleted within a 2 h incubation with 250 microM HNE. After removal of the aldehyde it was replenished by de novo synthesis leading to an overshooting GSH level, which later decreased to the basal level. In addition, trehalose was elevated 4-fold in HNE-treated yeast cells compared to control cells. We conclude that increased GSH levels upon HNE treatment are a general phenomenon of eukaryotic cells to ensure protection and survival during further harsh conditions. Furthermore, we have discovered a new indication for the stress marker trehalose in S. cerevisiae.

Aldehydes↗