The plasma compartment has particular features regarding the nature and concentration of low and high molecular weight thiols and oxidized derivatives. Plasma is relatively poor in thiol-based ...antioxidants; thiols are in lower concentrations than in cells and mostly oxidized. The different thiol-disulfide pairs are not in equilibrium and the steady-state concentrations of total thiols as well as reduced versus oxidized ratios are maintained by kinetic barriers, including the rates of reactions and transport processes. The single thiol of human serum albumin (HSA-SH) is the most abundant plasma thiol. It is an important target for oxidants and electrophiles due to its reactivity with a wide variety of species and its relatively high concentration. A relatively stable sulfenic (HSA-SO₃H) acid can be formed in albumin exposed to oxidants. Plasma increases in mixed disulfides (HSA-SSR) or in sulfinic (HSA-SO₂H) and sulfonic (HSA-SO₃H) acids are associated with different pathologies and may constitute biomarkers of the antioxidant role of the albumin thiol. In this work we provide a critical review of the plasma thiol pool with a focus on human serum albumin.
Signaling by H2S is proposed to occur via persulfidation, a posttranslational modification of cysteine residues (RSH) to persulfides (RSSH). Persulfidation provides a framework for understanding the ...physiological and pharmacological effects of H2S. Due to the inherent instability of persulfides, their chemistry is understudied. In this review, we discuss the biologically relevant chemistry of H2S and the enzymatic routes for its production and oxidation. We cover the chemical biology of persulfides and the chemical probes for detecting them. We conclude by discussing the roles ascribed to protein persulfidation in cell signaling pathways.
Hydrogen sulfide (H2S) has been traditionally considered to be a toxic molecule for mammals. However, it can be formed endogenously and exert physiological effects with potential health benefits. H2S ...can partition two-fold in biological membranes and traverse them rapidly, diffusing between compartments. H2S reactivity has similarities to that of thiols, although it is less nucleophilic than thiols and it can form different products. H2S can react with oxidants derived from the partial reduction of oxygen, but direct scavenging is unlikely to explain H2S protective actions. Important effects are exerted on mitochondria including the stimulation or the inhibition of the electron transport chain. Possible mechanisms for unleashing biological consequences are the reactions with metal centers and with thiol oxidation products. The reactions of H2S with disulfides (RSSR) and sulfenic acids (RSOH) lead to the formation of persulfides (RSSH). Persulfides have enhanced nucleophilicity with respect to the corresponding thiol, consistent with the alpha effect. Besides, the inner and outer sulfurs can both act as electrophiles. In this review, we describe the reactions of H2S with oxidized thiol products and the properties of the persulfides formed in the context of the chemical biology of H2S.
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•H2S can be formed in mammalian tissues and exert physiological effects.•H2S is less nucleophilic than thiols and can form particular products.•H2S can react with metal centers and thiol oxidation products (RSSR and RSOH).•Persulfides (RSSH) can be formed through H2S-dependent and independent pathways.•Persulfides are strong nucleophiles and weak electrophiles.
The oxidation of biothiols participates not only in the defense against oxidative damage but also in enzymatic catalytic mechanisms and signal transduction processes. Thiols are versatile reductants ...that react with oxidizing species by one- and two-electron mechanisms, leading to thiyl radicals and sulfenic acids, respectively. These intermediates, depending on the conditions, participate in further reactions that converge on different stable products. Through this review, we will describe the biologically relevant species that are able to perform these oxidations and we will analyze the mechanisms and kinetics of the one- and two-electron reactions. The processes undergone by typical low-molecular-weight thiols as well as the particularities of specific thiol proteins will be described, including the molecular determinants proposed to account for the extraordinary reactivities of peroxidatic thiols. Finally, the main fates of the thiyl radical and sulfenic acid intermediates will be summarized.
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Dostopno za:
BFBNIB, DOBA, GIS, IJS, IZUM, KILJ, KISLJ, NUK, PILJ, PNG, SAZU, UILJ, UKNU, UL, UM, UPUK
Peroxynitrite is a short-lived and reactive biological oxidant formed from the diffusion-controlled reaction of the free radicals superoxide (O2 •–) and nitric oxide (•NO). In this review, we first ...analyze the biochemical evidence for the formation of peroxynitrite in vivo and the reactions that lead to it. Then, we describe the principal reactions that peroxynitrite undergoes with biological targets and provide kinetic and mechanistic details. In these reactions, peroxynitrite has roles as (1) peroxide, (2) Lewis base, and (3) free radical generator. Physiological levels of CO2 can change the outcome of peroxynitrite reactions. The second part of the review assesses the formation of protein 3-nitrotyrosine (NO2Tyr) by peroxynitrite-dependent and -independent mechanisms, as one of the hallmarks of the actions of •NO-derived oxidants in biological systems. Moreover, tyrosine nitration impacts protein structure and function, tyrosine kinase signal transduction cascades and protein turnover. Overall, the review is aimed to provide an integrated biochemical view on the formation and reactions of peroxynitrite under biologically relevant conditions and the impact of this stealthy oxidant and one of its major footprints, protein NO2Tyr, in the disruption of cellular homeostasis.
The present study aimed to examine the effects of the Spanish confinement derived from the COVID-19 crisis on children and their families, accounting for child's age. A range of child negative (e.g., ...conduct problems) and positive outcomes (e.g., routine maintenance) were examined, along with a set of parent-related variables, including resilience, perceived distress, emotional problems, parenting distress and specific parenting practices (e.g., structured or avoidant parenting), which were modeled through path analysis to better understand child adjustment. Data were collected in April 2020, with information for the present study provided by 940 (89.6%) mothers, 102 (9.7%) fathers and 7 (0.7%) different caregivers, who informed on 1049 Spanish children (50.4% girls) aged 3 to 12 years (M
= 7.29; SD = 2.39). The results suggested that, according to parents' information, most children did not show important changes in behavior, although some increasing rates were observed for both negative and positive outcomes. Child adjustment was influenced by a chain of effects, derived from parents' perceived distress and emotional response to the COVID-19 crisis, via parenting distress and specific parenting practices. While parenting distress in particular triggered child negative outcomes, specific parenting practices were more closely related to child positive outcomes. These findings may help to better inform, for potential future outbreaks, effective guidelines and prevention programs aimed at promoting the child's well-being in the family.
The presence of cell walls entrapping starch granules in common bean cotyledons, prevailing after thermal processing and mechanical disintegration, has been identified as the main reason for their ...(s)low in vitro starch digestibility. Nevertheless, it is unknown if the role of cell walls on starch digestion changes as processing conditions (e.g. time) are modified. In this study, it was hypothesised that cell wall permeability would be differently affected depending on thermal process intensity, giving origin to distinct in vitro starch digestion kinetic profiles. Cotyledon cells were isolated from common beans by applying processing conditions normally found at the household level (95 °C and times between 30 and 180 min (palatable range)). Isolated cells were characterised and subsequently subjected to in vitro simulated digestion. Microstructural properties, the starch gelatinisation degree, and the total starch content were similar among samples. In contrast, a higher diffusion of fluorescently labelled pancreatic α-amylase inside the cells was evident as processing time increased. From the kinetic analysis of digestion products, it was determined that longer lag phases and slower reaction rate constants were present in samples with a lower degree of process-induced cell wall permeability. The qualitative analysis of the remaining pellets showed that cellular integrity was maintained throughout in vitro digestion. A mechanism for the in vitro starch digestion of isolated common bean cotyledon cells as well as an alternative kinetic model to describe this process were proposed. Overall, our work demonstrated that the in vitro starch digestion kinetics of common bean cotyledon cells can be modulated by influencing cell wall permeability through thermal processing time.
The use of non-occupational post-exposure prophylaxis (nPEP) emerges as a strategic intervention to reduce HIV infection risk following sexual encounters in our setting. Notwithstanding, there is a ...scarcity of contemporary data regarding adherence to this treatment, its effectiveness and tolerance. Our study aims to delve into these factors among individuals who have resorted to nPEP after high-risk sexual encounters.
We conducted a retrospective observational study of cases administered nPEP for HIV from 1 January 2018 to 31 December 2021 at a tertiary hospital in Madrid. The study included all adults over 18 years who sought care at the emergency department of the Fundación Jiménez Díaz Hospital following a risky sexual encounter and were subsequently recommended HIV nPEP treatment.
878 individuals received nPEP for HIV and underwent initial serological tests. Of these, 621 had comprehensive follow-ups. The prescribed regimen for all was raltegravir (RAL) 1200 mg combined with tenofovir/emtricitabine (TDF/FTC) 245/200 mg daily for 28 days. The study revealed a 1.1% rate (n=10) of previously undetected infection and a 0.16% (n=1) failure rate of nPEP. Regarding regimen tolerability, 5.6% (n=35) experienced symptoms linked to the treatment, yet none necessitated discontinuation of the regimen. On the contrary, six per cent (n=53) reported symptoms consistent with an STI during one of the medical visits; specifically, 4.4% had urethritis, and 1.6% had proctitis.
nPEP with RAL/TDF/FTC demonstrates high efficacy and safety, contingent on proper adherence. There is an observed increase in STI prevalence in this cohort, with nearly half of the participants not engaging in appropriate follow-up after initiating nPEP.
The COVID-19 pandemic has changed the lives of millions of people around the globe and some of the unprecedent emerged disruptions, are likely to have been particularly challenging for young children ...(e.g., school closures, social distancing measures, movement restrictions). Studying the impact of such extraordinary circumstances on their well-being is crucial to identify processes leading to risk and resilience. To better understand how Spanish children have adapted to the stressful disruptions resulting from the pandemic outbreak, we examined the effects of child coping and its interactions with contextual stressors (pandemic and family related) on child adjustment, incorporating in our analysis a developmental perspective. Data was collected in April 2020, through parent-reports, during the acute phase of the pandemic and, temporarily coinciding with the mandatory national quarantine period imposed by the Spanish Government. A sample of 1,123 Spanish children (50% girls) aged 3 to 12 (Mage = 7.26; SD = 2.39) participated in the study. Results showed differences in the use of specific strategies by children in different age groups (i.e., 3-6, 7-9 and 10-12-year-olds). Despite the uncontrollable nature of the pandemic-related stressors, child disengagement coping was distinctively associated to negative outcomes (i.e., higher levels of behavioral and emotional difficulties), whereas engagement coping predicted psychosocial adjustment across all age groups. Moreover, interactively with child coping, parent fear of the future and parent dispositional resilience appear as relevant contextual factors to predict both negative and positive outcomes, but their effects seem to be age dependent, suggesting a higher contextual vulnerability for younger children. These findings might have implications for identifying individual and contextual risk and informing potential preventive interventions aimed to reduce the impact of future pandemic outbreaks on children of different ages.
Persulfides (RSSH/RSS−) participate in sulfur trafficking and metabolic processes, and are proposed to mediate the signaling effects of hydrogen sulfide (H2S). Despite their growing relevance, their ...chemical properties are poorly understood. Herein, we studied experimentally and computationally the formation, acidity, and nucleophilicity of glutathione persulfide (GSSH/GSS−), the derivative of the abundant cellular thiol glutathione (GSH). We characterized the kinetics and equilibrium of GSSH formation from glutathione disulfide and H2S. A pKa of 5.45 for GSSH was determined, which is 3.49 units below that of GSH. The reactions of GSSH with the physiologically relevant electrophiles peroxynitrite and hydrogen peroxide, and with the probe monobromobimane, were studied and compared with those of thiols. These reactions occurred through SN2 mechanisms. At neutral pH, GSSH reacted faster than GSH because of increased availability of the anion and, depending on the electrophile, increased reactivity. In addition, GSS− presented higher nucleophilicity with respect to a thiolate with similar basicity. This can be interpreted in terms of the so-called α effect, i.e. the increased reactivity of a nucleophile when the atom adjacent to the nucleophilic atom has high electron density. The magnitude of the α effect correlated with the Brønsted nucleophilic factor, βnuc, for the reactions with thiolates and with the ability of the leaving group. Our study constitutes the first determination of the pKa of a biological persulfide and the first examination of the α effect in sulfur nucleophiles, and sheds light on the chemical basis of the biological properties of persulfides.
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