Perspective on Recent Developments on Sulfur-Containing Agents and Hydrogen Sulfide Signaling (original) (raw)
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Hydrogen sulfide mediates the vasoactivity of garlic
The consumption of garlic is inversely correlated with the progression of cardiovascular disease, although the responsible mechanisms remain unclear. Here we show that human RBCs convert garlic-derived organic polysulfides into hydrogen sulfide (H 2S), an endogenous cardioprotective vascular cell signaling molecule. This H 2S production, measured in real time by a novel polarographic H 2S sensor, is supported by glucosemaintained cytosolic glutathione levels and is to a large extent reliant on reduced thiols in or on the RBC membrane. H 2S production from organic polysulfides is facilitated by allyl substituents and by increasing numbers of tethering sulfur atoms. Allyl-substituted polysulfides undergo nucleophilic substitution at the ␣ carbon of the allyl substituent, thereby forming a hydropolysulfide (RS nH), a key intermediate during the formation of H 2S. Organic polysulfides (R-Sn-R; n > 2) also undergo nucleophilic substitution at a sulfur atom, yielding RS nH and H2S. Intact aorta rings, under physiologically relevant oxygen levels, also metabolize garlic-derived organic polysulfides to liberate H 2S. The vasoactivity of garlic compounds is synchronous with H 2S production, and their potency to mediate relaxation increases with H 2S yield, strongly supporting our hypothesis that H 2S mediates the vasoactivity of garlic. Our results also suggest that the capacity to produce H 2S can be used to standardize garlic dietary supplements.
Cell Biochemistry and Function, 2012
The aim of the present studies was to determine whether the mechanism of biological action of garlic-derived sulfur compounds in human hepatoma (HepG2) cells can be dependent on the presence of labile sulfane sulfur in their molecules. We investigated the effect of allyl sulfides from garlic: monosulfide, disulfide and trisulfide on cell proliferation and viability, caspase 3 activity and hydrogen peroxide (H 2 O 2 ) production in HepG2 cells. In parallel, we also examined the influence of the previously mentioned compounds on the levels of thiols, glutathione, cysteine and cysteinyl-glycine, and on the level of sulfane sulfur and the activity of its metabolic enzymes: rhodanese, 3-mercaptopyruvate sulfurtransferase and cystathionase. Among the compounds under study, diallyl trisulfide (DATS), a sulfane sulfur-containing compound, showed the highest biological activity in HepG2 cells. This compound increased the H 2 O 2 formation, lowered the thiol level and produced the strongest inhibition of cell proliferation and the greatest induction of caspase 3 activity in HepG2 cells. DATS did not affect the activity of sulfurtransferases and lowered sulfane sulfur level in HepG2 cells. It appears that sulfane sulfur containing DATS can be bioreduced in cancer cells to hydroperthiol that leads to H 2 O 2 generation, thereby influencing transmission of signals regulating cell proliferation and apoptosis. hydroperthiols with H 2 O 2 generation (Scheme 3). Sulfane sulfur from thiosulfoxide, which is a DADS isomer, does not show such properties. It indicates that only sulfane sulfur released from DATS in the form of hydroperthiol can produce biological activity in HepG2 cells restoring redox regulation, and this is not accompanied by formation of hydropersulfides of proteins.
Health Benefits of Plant-Derived Sulfur Compounds, Glucosinolates, and Organosulfur Compounds
Molecules
The broad spectrum of the mechanism of action of immune-boosting natural compounds as well as the complex nature of the food matrices make researching the health benefits of various food products a complicated task. Moreover, many routes are involved in the action of most natural compounds that lead to the inhibition of chronic inflammation, which results in a decrease in the ability to remove a pathogen asymptomatically and is connected to various pathological events, such as cancer. A number of cancers have been associated with inflammatory processes. The current review strives to answer the question of whether plant-derived sulfur compounds could be beneficial in cancer prevention and therapy. This review focuses on the two main sources of natural sulfur compounds: alliaceous and cruciferous vegetables. Through the presentation of scientific data which deal with the study of the chosen compounds in cancer (cell lines, animal models, and human studies), the discussion of food proc...
Physiological and pharmacological features of the novel gasotransmitter: Hydrogen sulfide
Biochimica et Biophysica Acta (BBA) - Bioenergetics, 2009
Hydrogen sulfide (H 2 S) has been known for hundreds of years because of its poisoning effect. Once the basal bio-production became evident its pathophysiological role started to be investigated in depth. H 2 S is a gas that can be formed by the action of two enzymes, cystathionine gamma-lyase and cystathionine betasynthase, both involved in the metabolism of cysteine. It has several features in common with the other two well known "gasotransmitters" (nitric oxide and carbon monoxide) in the biological systems. These three gasses share some biological targets; however, they also have dissimilarities. For instance, the three gases target heme-proteins and open K ATP channels; H 2 S as NO is an antioxidant, but in contrast to the latter molecule, H 2 S does not directly form radicals. In the last years H 2 S has been implicated in several physiological and pathophysiological processes such as long term synaptic potentiation, vasorelaxation, proand anti-inflammatory conditions, cardiac inotropism regulation, cardioprotection, and several other physiological mechanisms. We will focus on the biological role of H 2 S as a molecule able to trigger cell signaling. Our attention will be particularly devoted on the effects in cardiovascular system and in cardioprotection. We will also provide available information on H 2 S-donating drugs which have so far been tested in order to conjugate the beneficial effect of H 2 S with other pharmaceutical properties.
Sulfide regulation of cardiovascular function in health and disease
Nature Reviews Cardiology
Hydrogen sulfide (H 2 S) has emerged as a gaseous signalling molecule with crucial implications for cardiovascular health. H 2 S is involved in many biological functions, including interactions with nitric oxide, activation of molecular signalling cascades, post-translational modifications and redox regulation. Various preclinical and clinical studies have shown that H 2 S and its synthesizing enzymes-cystathionine γ-lyase, cystathionine β-synthase and 3-mercaptosulfotransferase-can protect against cardiovascular pathologies, including arrhythmias, atherosclerosis, heart failure, myocardial infarction and ischaemia-reperfusion injury. The bioavailability of H 2 S and its metabolites, such as hydropersulfides and polysulfides, is substantially reduced in cardiovascular disease and has been associated with single-nucleotide polymorphisms in H 2 S synthesis enzymes. In this Review, we highlight the role of H 2 S, its synthesizing enzymes and metabolites, their roles in the cardiovascular system, and their involvement in cardiovascular disease and associated pathologies. We also discuss the latest clinical findings from the field and outline areas for future study.
Journal of applied botany and food quality, 2019
Plant-derived sulfur-containing secondary metabolites constitute a small group of low-molecular weight natural products, which play a vital role in plant-pest interactions in numerous plant families andrepresent major defense molecules in the Asteraceae, Alliaceae, and Brassicaceae families. In this review we highlight the crucial role of environmental stress factors in the production of S-containing secondary metabolites. Furthermore, we describe a serendipitous variety of plant-derived sulfur-containing natural products produced or induced under biotic and abiotic stress and their structural diversity, promising pharmacological properties for use by humans, and beneficial effects for plants. Specifically, cruciferous phytoalexins are known as elicit plant defense molecules. Glucosinolates are candidates for tumorpreventive effects. Cysteine sulfoxides found in garlic are considered as profound antimicrobial agents. In this review, we discuss types of S bonds in the molecules and t...