One- and Two-Electron Oxidations of β-Amyloid_25-35 by Carbonate Radical Anion (CO₃•-) and Peroxymonocarbonate (HCO₄-):Role of Sulfur in Radical Reactions and Peptide Aggregation

The β-amyloid (Aβ) peptide plays a key role in the pathogenesis of Alzheimer’s disease. The methionine (Met) residue at position 35 in Aβ C-terminal domain is critical for neurotoxicity, aggregation, and free radical formation initiated by the peptide. The role of Met in modulating toxicological properties of Aβ most likely involves an oxidative event at the sulfur atom. We therefore investigated the one- or two-electron oxidation of the Met residue of Aβ25-35 fragment and the effect of such oxidation on the behavior of the peptide. Bicarbonate promotes two-electron oxidations mediated by hydrogen peroxide after generation of peroxymonocarbonate (HCO4−, PMC). The bicarbonate/carbon dioxide pair stimulates one-electron oxidations mediated by carbonate radical anion (CO3•−). PMC efficiently oxidizes thioether sulfur of the Met residue to sulfoxide. Interestingly, such oxidation hampers the tendency of Aβ to aggregate. Conversely, CO3•− causes the one-electron oxidation of methionine residue to sulfur radical cation (MetS•+). The formation of this transient reactive intermediate during Aβ oxidation may play an important role in the process underlying amyloid neurotoxicity and free radical generation

Risk factors for severe reactions in food allergy: Rapid evidence review with meta‐analysis

This rapid review summarizes the most up to date evidence about the risk factors for severe food-induced allergic reactions. We searched three bibliographic databases for studies published between January 2010 and August 2021. We included 88 studies and synthesized the evidence narratively, undertaking meta-analysis where appropriate. Significant uncertainties remain with respect to the prediction of severe reactions, both anaphylaxis and/or severe anaphylaxis refractory to treatment. Prior anaphylaxis, an asthma diagnosis, IgE sensitization or basophil activation tests are not good predictors. Some molecular allergology markers may be helpful. Hospital presentations for anaphylaxis are highest in young children, yet this age group appears at lower risk of severe outcomes. Risk of severe outcomes is greatest in adolescence and young adulthood, but the contribution of risk taking behaviour in contributing to severe outcomes is unclear. Evidence for an impact of cofactors on severity is lacking, although food-dependent exercise-induced anaphylaxis may be an exception. Some medications such as beta-blockers or ACE inhibitors may increase severity, but appear less important than age as a factor in life-threatening reactions. The relationship between dose of exposure and severity is unclear. Delays in symptom recognition and anaphylaxis treatment have been associated with more severe outcomes. An absence of prior anaphylaxis does not exclude its future risk

Thiotaurine modulates human neutrophil activation

Neutrophils are well recognized as one of the major players during acute infl ammation.They are typically the fi rst leukocytes to be recruited to an infl ammatory site and can eliminate pathogens by multiple means. Two different microbicidal mechanisms occur within the neutrophils: the oxidative and the non oxidative systems. The oxygen-dependent mechanism acts through generation of reactive oxygen species (ROS), and the oxygen-independent mechanism acts through production of antimicrobial peptides and proteolytic enzymes. During infl ammation, neutrophils are activated in response to several agonists generating superoxide anion and other ROS by NADPH oxidase-dependent mechanisms. This functional response, termed oxidative burst, contributes to host defense, but it can also result in collateral damage of host tissues. NADPH oxidase is a multicomponent enzyme system that catalyzes NADPH-dependent reduction of oxygen to superoxide anion. NADPH oxidase is activated by a variety of agents including N -formyl-methionyl-leucyl-phenylalanine (fMLP) and the protein kinase C (PKC) activator phorbol 12-myristate 13-acetate (PMA). These stimuli trigger biochemical cascades leading to the phosphorylation of several proteins of the NADPH oxidase system. In addition to the well-documented PKC pathway, one of these cascades involves activation of members of the mitogen-activated protein kinase (MAPK) family. Several studies have demonstrated that MAPK pathways such as extracellular signal- regulated kinases (ERK) 1/2 and p38 MAPK are activated in human neutrophils. Taurine is the most abundant free amino acid in most animal tissues and plays an important role in several essential biological processes (Huxtable 1992 ). A large number of reports have demonstrated the key role of taurine and its derivatives in the innate immune response (Schuller-Levis and Park 2004 ). It is widely recognized that taurine and related compounds such as hypotaurine and taurine chloramine exert a regulatory role in acute infl ammation. The protection by taurine and its derivatives on infl ammatory injury may be due to modulation of NADPH oxidase activity. It is noteworthy that taurine chloramines decrease PMA-stimulated superoxide production in human neutrophils by inhibiting phosphorylation of subunits of NADPH oxidase, eventually blocking the assembly of NADPH oxidase complex. Recently, it has been shown that thiotaurine (2-aminoethane thiosulfonate), a biomolecule structurally related to hypotaurine and taurine, prevents spontaneous apoptosis of human neutrophils (Capuozzo et al. 2013 ) and counteracts the damaging effect of oxidants in diabetic rat (Budhram et al. 2013 ). Interestingly, thiotaurine contains a sulfane sulfur that can be released as hydrogen sulfi de (H 2 S). It has been shown that H 2 S plays relevant roles, modulating several pathophysiological processes, including infl ammation. Taken together, these observations raise the possibility that thiotaurine, analogously to taurine and its derivatives, could modulate neutrophil activation. Thiotaurine is a thiosulfonates (RSO 2 SH) which has been occasionally detectedamong the products of biochemical reactions involving sulfur compounds. Thiotaurine is a metabolic product of cysteine in vivo and is produced by a spontaneous transsulfuration reaction involving thiocysteine (RSSH) and hypotaurine (RSO2H). Moreover, a sulfurtransferase which catalyzes the transfer of sulfur from mercaptopyruvate to hypotaurine with production of thiotaurine has been also reported. In the present study, thiotaurine has been assessed for an activity on functional response of human neutrophils. The results reveal that thiotaurine modulates fMLP- and PMA-mediated activation of human neutrophils, by inhibiting total ROS generation and superoxide anion production. Compared with fMLP-activated neutrophils, PMA-activated neutrophils were more susceptible to thiotaurine inhibition, suggesting that thiotaurine may interfere with the PKC-dependent pathway of neutrophil activation

Editorial for Special Issue on “Regulation and Effect of Taurine on Metabolism”

Taurine (2-aminoethanesulfonic acid) is well known to be abundantly contained in almost all the tissues and cells of various mammals, fish, and shellfish [...

Chemistry and Biochemistry of Sulfur Natural Compounds: Key Intermediates of Metabolism and Redox Biology

Sulfur contributes significantly to nature chemical diversity and thanks to its particular features allows fundamental biological reactions that no other element allows. Sulfur natural compounds are utilized by all living beings and depending on the function are distributed in the different kingdoms. It is no coincidence that marine organisms are one of the most important sources of sulfur natural products since most of the inorganic sulfur is metabolized in ocean environments where this element is abundant. Terrestrial organisms such as plants and microorganisms are also able to incorporate sulfur in organic molecules to produce primary metabolites (e.g., methionine, cysteine) and more complex unique chemical structures with diverse biological roles. Animals are not able to fix inorganic sulfur into biomolecules and are completely dependent on preformed organic sulfurous compounds to satisfy their sulfur needs. However, some higher species such as humans are able to build new sulfur-containing chemical entities starting especially from plants’ organosulfur precursors. Sulfur metabolism in humans is very complicated and plays a central role in redox biochemistry. The chemical properties, the large number of oxidation states, and the versatile reactivity of the oxygen family chalcogens make sulfur ideal for redox biological reactions and electron transfer processes. This review will explore sulfur metabolism related to redox biochemistry and will describe the various classes of sulfur-containing compounds spread all over the natural kingdoms. We will describe the chemistry and the biochemistry of well-known metabolites and also of the unknown and poorly studied sulfur natural products which are still in search for a biological role