Endogenous sulfur dioxide deficiency as a driver of cardiomyocyte senescence through abolishing sulphenylation of STAT3 at cysteine 259.

OBJECTIVE: Cardiomyocyte senescence is an important contributor to cardiovascular diseases and can be induced by stressors including DNA damage, oxidative stress, mitochondrial dysfunction, epigenetic regulation, etc. However, the underlying mechanisms for the development of cardiomyocyte senescence remain largely unknown. Sulfur dioxide (SO2) is produced endogenously by aspartate aminotransferase 2 (AAT2) catalysis and plays an important regulatory role in the development of cardiovascular diseases. The present study aimed to explore the effect of endogenous SO2 on cardiomyocyte senescence and the underlying molecular mechanisms. APPROACH AND RESULTS: We interestingly found a substantial reduction in the expression of AAT2 in the heart of aged mice in comparison to young mice. AAT2-knockdowned cardiomyocytes exhibited reduced SO2 content, elevated expression levels of Tp53, p21Cip/Waf, and p16INk4a, enhanced SA-ß-Gal activity, and elevated level of γ-H2AX foci. Notably, supplementation with a SO2 donor ameliorated the spontaneous senescence phenotype and DNA damage caused by AAT2 deficiency in cardiomyocytes. Mechanistically, AAT2 deficiency suppressed the sulphenylation of signal transducer and activator of transcription 3 (STAT3) facilitated its nuclear translocation and DNA-binding capacity. Conversely, a mutation in the cysteine (Cys) 259 residue of STAT3 blocked SO2-induced STAT3 sulphenylation and subsequently prevented the inhibitory effect of SO2 on STAT3-DNA-binding capacity, DNA damage, and cardiomyocyte senescence. Additionally, cardiomyocyte (cm)-specific AAT2 knockout (AAT2cmKO) mice exhibited a deterioration in cardiac function, cardiomegaly, and cardiac aging, whereas supplementation with SO2 donors mitigated the cardiac aging and remodeling phenotypes in AAT2cmKO mice. CONCLUSION: Downregulation of the endogenous SO2/AAT2 pathway is a crucial pathogenic mechanism underlying cardiomyocyte senescence. Endogenous SO2 modifies STAT3 by sulphenylating Cys259, leading to the inhibition of DNA damage and the protection against cardiomyocyte senescence.

Endogenous Sulfur Dioxide Inhibits Vascular Calcification in Association with the TGF-ß/Smad Signaling Pathway.

The study was designed to investigate whether endogenous sulfur dioxide (SO2) plays a role in vascular calcification (VC) in rats and its possible mechanisms. In vivo medial vascular calcification was induced in rats by vitamin D3 and nicotine for four weeks. In vitro calcification of cultured A7r5 vascular smooth muscle cells (VSMCs) was induced by calcifying media containing 5 mmol/L CaCl2. Aortic smooth muscle (SM) α-actin, runt-related transcription factor 2 (Runx2), transforming growth factor-ß (TGF-ß) and Smad expression was measured. VC rats showed dispersed calcified nodules among the elastic fibers in calcified aorta with increased aortic calcium content and alkaline phosphatase (ALP) activity. SM α-actin was markedly decreased, but the osteochondrogenic marker Runx2 concomitantly increased and TGF-ß/Smad signaling was activated, in association with the downregulated SO2/aspartate aminotransferase (AAT) pathway. However, SO2 supplementation successfully ameliorated vascular calcification, and increased SM α-actin expression, but inhibited Runx2 and TGF-ß/Smad expression. In calcified A7r5 VSMCs, the endogenous SO2/AAT pathway was significantly downregulated. SO2 treatment reduced the calcium deposits, calcium content, ALP activity and Runx2 expression and downregulated the TGF-ß/Smad pathway in A7r5 cells but increased SM α-actin expression. In brief, SO2 significantly ameliorated vascular calcification in association with downregulation of the TGF-ß/Smad pathway.

Effects of atmospheric pollutants (CO, O3, SO2) on the allergenicity of Betula pendula, Ostrya carpinifolia, and Carpinus betulus pollen.

Pollen of Betula pendula, Ostrya carpinifolia, and Carpinus betulus was exposed in vitro to relatively low levels of the air pollutants, namely carbon monoxide, ozone, and sulfur dioxide. The allergenicity of the exposed pollen was compared with that of non-exposed pollen samples to assess if air pollution exposition affects the allergenicity potential of pollen. The immunodetection assays indicated higher IgE recognition by all sera of allergic patients to the pollen protein extracts in all exposed samples in comparison to the non-exposed samples. These results show that the pollen exposition to low pollutants' levels induces increased allergic reaction to sensitized individuals.

Effect of CO, NOx and SO2 on ROS production, photosynthesis and ascorbate-glutathione pathway to induce Fragaria×annasa as a hyperaccumulator.

A study was conducted to determine the effect of carbon monoxide (CO), nitroxide (NOx) and sulfur dioxide (SO2) on ROS production, photosynthesis and ascorbate-glutathione pathway in strawberry plants. The results showed that both singlet oxygen (O2(-1)) and hydrogen peroxide (H2O2) content increased in CO, NOx and SO2 treated strawberry leaves. A drastic reduction of primary metabolism of plants (photosynthesis), with the closure of stomata, resulted in a reduction of protein, carbohydrate and sucrose content due to production of reactive oxygen species (ROS) under prolonged exposure of gas stress. The resulting antioxidant enzymes were increased under a low dose of gas stress, whereas they were decreased due to a high dose of gas stress. Our results indicate that increased ROS may act as a signal to induce defense responses to CO, NOx and SO2 gas stress. The increased level of antioxidant enzymes plays a significant role in plant protection due to which strawberry plants can be used as a hyperaccumulator to maintain environmental pollution, however, the defense capacity cannot sufficiently alleviate oxidative damage under prolonged exposure of CO, NOx and SO2 stress.

Effect of wine inhibitors on free pineapple stem bromelain activity in a model wine system.

The influence of potential inhibitors, naturally present in wine, on the activity of stem bromelain was investigated in order to evaluate the applicability of this enzyme for protein stabilization in white wine. Bromelain proteolytic activity was tested against a synthetic substrate (Bz-Phe-Val-Arg-pNA) in a model wine system after adding ethanol, sulfur dioxide (SO(2)), skin, seed, and gallic and ellagic tannins at the average range of their concentration in wine. All the inhibitors of stem bromelain activity tested turned out to be reversible. Ethanol was a competitive inhibitor with a rather limited effect. Gallic and ellagic tannins have no inhibitory effect on stem bromelain activity, while both seed and skin tannins were uncompetitive inhibitors. The strongest inhibition effect was revealed for sulfur dioxide, which was a mixed-type inhibitor for the enzyme activity. This study provides useful information relative to a future biotechnological application of stem bromelain in winemaking.

Stomatal index responses of Agrostis canina to CO2 and sulphur dioxide: implications for palaeo-[CO2] using the stomatal proxy.

• Stomatal index values of fossil plants are widely used in reconstructing palaeo-[CO(2)]. This depends upon the assumption that the stomatal index is determined by the atmospheric concentration of CO(2) ([CO(2)]). This study investigates whether fumigation with, and resistance to, sulphur dioxide (SO(2)) induces a reduction in the stomatal index that may affect stomatal reconstructions of palaeo-[CO(2)] coinciding with episodes of global-scale volcanism. • Agrostis canina from Mefite di Ansanto, Italy, grow in atmospheres of elevated-[CO(2)], SO(2) and hydrogen sulphide (H(2)S). Mefite A. canina were compared with a control population in a 'common-garden' experiment and a controlled-environment study under elevated-[CO(2)] and SO(2) fumigation. • In A. canina, resistance to toxic volcanic gases is not associated with reduced stomatal index, and fumigation with SO(2) does not cause a decrease in stomatal initiation. The two populations of A. canina analyzed in this study exhibit different stomatal index-[CO(2)] 'responses', with control plants showing a reduction in stomatal index and Mefite plants showing no response. • Stomatal reconstructions of palaeo-[CO(2)] during past episodes of global-scale volcanism probably reflect atmospheric [CO(2)] and not [SO(2)]. The lack of a reduction in the stomatal index in response to elevated [CO(2)] in the Mefite plants, suggests that resistance to toxic gases and/or long-term growth at high [CO(2)] reduces, or negates, sensitivity of the stomatal index-[CO(2)] relationship, or that stomatal index-[CO(2)] in the Mefite plants is attuned to [CO(2)] fluctuations at much higher concentrations.

Risk of asthmatic episodes in children exposed to sulfur dioxide stack emissions from a refinery point source in Montreal, Canada.

BACKGROUND: Little is known about the respiratory effects of short-term exposures to petroleum refinery emissions in young children. This study is an extension of an ecologic study that found an increased rate of hospitalizations for respiratory conditions among children living near petroleum refineries in Montreal (Canada). METHODS: We used a time-stratified case-crossover design to assess the risk of asthma episodes in relation to short-term variations in sulfur dioxide levels among children 2-4 years of age living within 0.5-7.5 km of the refinery stacks. Health data used to measure asthma episodes included emergency department (ED) visits and hospital admissions from 1996 to 2004. We estimated daily levels of SO2 at the residence of children using a) two fixed-site SO2 monitors located near the refineries and b) the AERMOD (American Meteorological Society/Environmental Protection Agency Regulatory Model) atmospheric dispersion model. We used conditional logistic regression to estimate odds ratios associated with an increase in the interquartile range of daily SO2 mean and peak exposures (31.2 ppb for AERMOD peaks). We adjusted for temperature, relative humidity, and regional/urban background air pollutant levels. RESULTS: The risks of asthma ED visits and hospitalizations were more pronounced for same-day (lag 0) SO2 peak levels than for mean levels on the same day, or for other lags: the adjusted odds ratios estimated for same-day SO2 peak levels from AERMOD were 1.10 [95% confidence interval (CI), 1.00-1.22] and 1.42 (95% CI, 1.10-1.82), over the interquartile range, for ED visits and hospital admissions, respectively. CONCLUSIONS: Short-term episodes of increased SO2 exposures from refinery stack emissions were associated with a higher number of asthma episodes in nearby children.

Control of rotting and browning of Longan fruit cv. Biew Kiew after harvested by sulphur dioxide treatment under various storage temperatures.

The experiment of Longan fruit cv. Biew Kiew, untreated (control) and treated with SO2 treatment were stored under 2 +/- 2 and 7 +/- 2 degrees C for 0, 2, 4, 6 and 8 weeks were studied. The treatment of fresh longan fruit with SO2 fumigation combined with the suitable storage condition improved the overall longan fruit quality, especially on inner and outer peel tissue and aril color than no SO2 treatment. Treatment stabilizes peel color with no subsequent loss of color during storage (fruit color were bright-yellowish color). When the fruit showed during SO2 treatment, increasing of storage duration and temperatures, the dark color of inner and outer peel of longan fruit was appeared, this was correlated with the increasing of PPO activity. The activity of PPO enzyme in control fruit (no SO2 treatment) gradually lower than SO2 treatments. Fruit exposed to cool storage temperature (2 degrees C) exhibited a lower PPO enzymatic activity compared to those kept in high storage temperature (7 degrees C). Moreover, PPO enzymatic activity significantly increased over the storage durations The additional SO2 treatment no subsequent loss of weight of longan fruit during storage. However, the sulphite residues could detect immediately after SO2 treatment in all part of longan fruit, especially on aril tissue. The SEM evaluation found that the surface cracking was also impair the physiological function of the cuticle and increasing water permeability, which may cause water soaking at the inner side of the peel. The injured cell would accelerate the oxidation of phenolic substances and the oxidative products resulted in dark color of inner and outer peel.

[Vasorelaxant effect of sulfur dioxide derivatives on isolated aortic rings of rats and its mechanisms].

OBJECTIVE: To investigate the vasorelaxant effect of sulfur dioxide (SO(2)) on isolated aortic rings of rats in vitro and its relaxation mechanisms. METHODS: We perffused the isolated aortic rings of rats, and precontracted the rings with noradrenaline (NE), then observed the relaxant reactivity of SO(2) derivatives, mixture of sulfite and hydrogen sulfite [Na(2)SO(3)/NaHSO(3) 3:1(amount of substance)], to the aortic rings. Meanwhile, we studied the influence of glibenclamide and nicardipine, blockers of K(ATP) and L-calcium channels, on the vasorelaxant reactivity of SO(2) derivatives. We further incubated the aortic rings with hydroxamate (HDX), the inhibitor of SO(2) endogenous generating enzymes, and SO(2) derivatives (4 mmol/L) in vitro, then observed the contraction of the aortic rings to NE. RESULTS: Isolated aortic rings of rats exhibited relaxant reactivity to Na(2)SO(3)/NaHSO(3) (0-12 mmol/L) in a concentration-dependent manner. IC(50) of the relaxation curve was (7.28+/-0.12) mmol/Lìand Emax was 78.79%+/-3.24%. Glibenclamide (1x10(-6) mol/L) inhibited the vasorelaxation to low dose Na(2)SO(3)/NaHSO(3) (6 mmol/L). Nicardipine (1x10(-9) mol/L) could decrease the contraction of the rings to NE, and even could inhibit the relaxation of Na(2)SO(3)/NaHSO(3) almost completely. The inhibition of the endogenous SO(2) production with HDX (1x10(-4) mol/L), resulted in an increase in the contraction of rings. The contraction curve to NE shifted to the left, and IC(50) also changed from (6.48+/-0.84)x10(-7) mol/L to (3.97+/-1.63)x10(-7) mol/L (P<0.01). However, after the incubation of aortic rings with Na(2)SO(3)/NaHSO(3) (4 mmol/L), the contraction curve to NE shifted to the right, and IC(50) changed from (6.48+/-0.84)x10(-7) mol/L to (4.93+/-0.81)x10(-5) mol/L (P<0.01). CONCLUSION: SO(2) could relax vascular smooth muscles, and the mechanism might be associated with calcium channels and K(ATP) channels, suggesting that endogenous SO(2) could modulate the cardiovascular function.

[Effects of SO2 on NO reduction with methanol over Ag/Al2O3 catalyst].

Ag/Al2O3 catalyst with 5% Ag loading was prepared by the single step sol-gel mixture method and the effects of adding SO2 to reaction feed on NO reduction by CH3OH over the catalyst was investigated in the presence of oxygen. The results showed that in the absence of SO2 and H2O the catalyst displayed lower activity temperature and higher N2O selectivity, which was attributed to the partial reduction of oxidized Ag into metallic Ag under reaction conditions. Selective catalytic reduction activity was not decreased but significantly increased, N2O formation was suppressed and most effective NO reduction temperature shifted to higher temperature by pre-sulfated Ag/Al2O3 or addition of SO2 to reaction mixture. XPS analysis showed that the sulfate-like species were formed by the effect of SO2.

Sulfur dioxide inhibits the sucrose carrier of the plant plasma membrane.

Plasma membrane vesicles were prepared by phase partition from a microsomal fraction of broad bean (Vicia faba L.) leaf. In order to study the effects of sodium sulfite on active uptake of sucrose, the vesicles were artificially energized by a transmembrane pH gradient (delta pH) and/or a transmembrane electrical gradient (delta psi). At 1 mM, sulfite strongly inhibited sucrose uptake but did not affect the two components of the proton motive force, delta pH (measured by dimethyloxazolidine dione) and delta psi (measured by tetraphenylphosphonium). Moreover, sulfite did not inhibit the proton-pumping ATPase of the plasma membrane vesicles. These data demonstrate that sulfite may inhibit transport of photoassimilates in plant by a direct inhibition of the sucrose carrier of the plasma membrane.

The effect of atmospheric pollution on Vitis vinifera L. pollen ultrastructure under natural conditions.

The ultrastructural modification of pollen grains in Vitis vinifera L. variety and hybrids in areas of SO2 atmospheric pollution (the main polluting SO2 usually reaches 2.72 mg/m3), nitrogen oxide, and other gases derived from noniron metal processing factories have been studied. Strains 1001 and 1002, resistant varieties, do not undergo ultrastructural modifications. Neuburger and Issabelle, medium resistant ones, have a heterogeneity in ultrastructural organization from normal forms to forms having both wall covers as well as the main organelles changed.

An improvement to the use of sulfur dioxide to induce cough in experimental animals.

In this study a new method has been developed to administer sulfur dioxide to experimental animals in order to induce cough for testing antitussives. Sulfur dioxide was packed into aerosol cans equipped with a 75 microliter dosage nozzle. Sulfur dioxide was diluted with the fluorocarbon mixture and the content varied from 15-19% w/w. The dose of the sulfur dioxide aerosol used was 75-225 microliter. Guinea pigs breathed sulfur dioxide for 20 sec from a special muzzle connected to the aerosol can. The frequency of coughing was counted for 10 min after the sulfur dioxide challenge. The test procedure utilized an initial dose of sulfur dioxide as a basic stimulus in order to make the animals sensitive to sulfur dioxide. There were quite large differencies in cough caused by the baseline irritation by sulfur dioxide, but 1 hr after the baseline irritation, a further sulfur dioxide challenge evoked a reliable and reproducible incidence of cough.

Effect of oil mists on the irritancy of sulfur dioxide. II. Motor oil.

This study examines the effect of sub-micrometer aerosols of motor oil on the irritant potency of sulfur dioxide. The increase in pulmonary flow resistance in guinea pigs was used as the bioassay of irritant response. When administered simultaneously, both unused and used motor oil protected against the irritant response to sulfur dioxide. This protective effect was lost when the oils had been previously reacted with sulfur dioxide. The additives used in the motor oil provided an equivalent protection when dissolved in a mineral oil which alone did not protect. Pre-exposure to motor oil did not provide protection. Sulfur dioxide and motor oil given together as a pre-exposure provided protection against further exposure to sulfur dioxide.