scholarly journals Characterization of the Inducible and Slow-Releasing Hydrogen Sulfide and Persulfide Donor P*: Insights into Hydrogen Sulfide Signaling

Antioxidants ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1049
Author(s):  
Modesta Trummer ◽  
Erwan Galardon ◽  
Anita Fischer ◽  
Stefan Toegel ◽  
Bernhard-Michael Mayer ◽  
...  
Keyword(s):  
Hydrogen Sulfide ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Antioxidant Properties ◽  
Heme Oxygenase 1 ◽  
Primary Chondrocytes ◽  
Sodium Hydrogen ◽  
Inflammatory Processes ◽  
Complex Chemistry

Hydrogen sulfide (H2S) is an important mediator of inflammatory processes. However, controversial findings also exist, and its underlying molecular mechanisms are largely unknown. Recently, the byproducts of H2S, per-/polysulfides, emerged as biological mediators themselves, highlighting the complex chemistry of H2S. In this study, we characterized the biological effects of P*, a slow-releasing H2S and persulfide donor. To differentiate between H2S and polysulfide-derived effects, we decomposed P* into polysulfides. P* was further compared to the commonly used fast-releasing H2S donor sodium hydrogen sulfide (NaHS). The effects on oxidative stress and interleukin-6 (IL-6) expression were assessed in ATDC5 cells using superoxide measurement, qPCR, ELISA, and Western blotting. The findings on IL-6 expression were corroborated in primary chondrocytes from osteoarthritis patients. In ATDC5 cells, P* not only induced the expression of the antioxidant enzyme heme oxygenase-1 via per-/polysulfides, but also induced activation of Akt and p38 MAPK. NaHS and P* significantly impaired menadione-induced superoxide production. P* reduced IL-6 levels in both ATDC5 cells and primary chondrocytes dependent on H2S release. Taken together, P* provides a valuable research tool for the investigation of H2S and per-/polysulfide signaling. These data demonstrate the importance of not only H2S, but also per-/polysulfides as bioactive signaling molecules with potent anti-inflammatory and, in particular, antioxidant properties.

scholarly journals Cocoa Flavanols: Natural Agents with Attenuating Effects on Metabolic Syndrome Risk Factors

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 751 ◽  
Author(s):  
Maria Jaramillo Flores
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Antioxidant Properties ◽  
Laboratory Animals ◽  
Protective Effects ◽  
Plant Metabolites ◽  
Secondary Plant Metabolites

The interest in cacao flavanols is still growing, as bioactive compounds with potential benefits in the prevention of chronic diseases associated with inflammation, oxidative stress and metabolic disorders. Several analytical methodologies support that the flavanols in cacao-derived products can be absorbed, have bioactive properties, and thus can be responsible for their beneficial effects on human health. However, it must be considered that their biological actions and underlying molecular mechanisms will depend on the concentrations achieved in their target tissues. Based on the antioxidant properties of cacao flavanols, this review focuses on recent advances in research regarding their potential to improve metabolic syndrome risk factors. Additionally, it has included other secondary plant metabolites that have been investigated for their protective effects against metabolic syndrome. Studies using laboratory animals or human subjects represent strong available evidence for biological effects of cacao flavanols. Nevertheless, in vitro studies are also included to provide an overview of these phytochemical mechanisms of action. Further studies are needed to determine if the main cacao flavanols or their metabolites are responsible for the observed health benefits and which are their precise molecular mechanisms.

scholarly journals Heme-Oxygenase-1 Attenuates Oxidative Functions of Antigen Presenting Cells and Promotes Regulatory T Cell Differentiation during Fasciola hepatica Infection

Antioxidants ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1938
Author(s):  
Monique Costa ◽  
Valeria da Costa ◽  
Sofía Frigerio ◽  
María Florencia Festari ◽  
Mercedes Landeira ◽  
...  
Keyword(s):  
Heme Oxygenase ◽  
Molecular Mechanisms ◽  
Fasciola Hepatica ◽  
Antioxidant Properties ◽  
Antigen Presenting Cells ◽  
Parasite Infection ◽  
Economic Losses ◽  
Heme Oxygenase 1 ◽  
Host Immune System ◽  
Antigen Presenting

Fasciola hepatica is a fluke that infects livestock and humans causing fasciolosis, a zoonotic disease of increasing importance due to its worldwide distribution and high economic losses. The parasite regulates the host immune system by inducing a strong Th2 and regulatory T (Treg) cell immune response through mechanisms that might involve the expression or activity of heme-oxygenase-1 (HO-1), the rate-limiting enzyme in the catabolism of free heme that also has immunoregulatory and antioxidant properties. In this paper, we show that F. hepatica-infected mice upregulate HO-1 on peritoneal antigen-presenting cells (APC), which produce decreased levels of both reactive oxygen and nitrogen species (ROS/RNS). The presence of these cells was associated with increased levels of regulatory T cells (Tregs). Blocking the IL-10 receptor (IL-10R) during parasite infection demonstrated that the presence of splenic Tregs and peritoneal APC expressing HO-1 were both dependent on IL-10 activity. Furthermore, IL-10R neutralization as well as pharmacological treatment with the HO-1 inhibitor SnPP protected mice from parasite infection and allowed peritoneal APC to produce significantly higher ROS/RNS levels than those detected in cells from infected control mice. Finally, parasite infection carried out in gp91phox knockout mice with inactive NADPH oxidase was associated with decreased levels of peritoneal HO-1+ cells and splenic Tregs, and partially protected mice from the hepatic damage induced by the parasite, revealing the complexity of the molecular mechanisms involving ROS production that participate in the complex pathology induced by this helminth. Altogether, these results contribute to the elucidation of the immunoregulatory and antioxidant role of HO-1 induced by F. hepatica in the host, providing alternative checkpoints that might control fasciolosis.

scholarly journals Formation of 4-hydroxynonenal and further aldehydic mediators of inflammation during bromotrichlorornethane treatment of rat liver cells

1993 ◽  
Vol 2 (1) ◽  
pp. 27-31 ◽  
Author(s):  
Olaf Sommerburg ◽  
Tilman Grune ◽  
Sabine Klee ◽  
Fritz R. Ungemach ◽  
Werner G. Siems
Keyword(s):  
Lipid Peroxidation ◽  
Rat Liver ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Rat Hepatocytes ◽  
Liver Cells ◽  
Mediators Of Inflammation ◽  
Rat Liver Cells ◽  
Inflammatory Processes

Bromotrichloromethane (CBrCl3) treatment is a model for studies on molecular mechanisms of haloalkane toxicity with some advantages compared with CCl4treatment. The formation of 4-hydroxynonenal and similar aldehydic products of lipid peroxidation, which play a role as mediators of inflammatory processes, was clearly demonstrated in rat hepatocytes treated with CBrCl3. It may be assumed that haloalkane toxicity is connected with the biological effects of those inflammation mediatory aldehydic compounds.

scholarly journals A Systems Biology Overview on Human Diabetic Nephropathy: From Genetic Susceptibility to Post-Transcriptional and Post-Translational Modifications

2016 ◽  
Vol 2016 ◽  
pp. 1-23 ◽  
Author(s):  
Francesca Conserva ◽  
Loreto Gesualdo ◽  
Massimo Papale
Keyword(s):  
Diabetic Nephropathy ◽  
Systems Biology ◽  
Genetic Susceptibility ◽  
Molecular Mechanisms ◽  
Disease Onset ◽  
Systematic Analysis ◽  
Post Translational Modifications ◽  
Inflammatory Processes ◽  
End Stage

Diabetic nephropathy (DN), a microvascular complication occurring in approximately 20–40% of patients with type 2 diabetes mellitus (T2DM), is characterized by the progressive impairment of glomerular filtration and the development of Kimmelstiel-Wilson lesions leading to end-stage renal failure (ESRD). The causes and molecular mechanisms mediating the onset of T2DM chronic complications are yet sketchy and it is not clear why disease progression occurs only in some patients. We performed a systematic analysis of the most relevant studies investigating genetic susceptibility and specific transcriptomic, epigenetic, proteomic, and metabolomic patterns in order to summarize the most significant traits associated with the disease onset and progression. The picture that emerges is complex and fascinating as it includes the regulation/dysregulation of numerous biological processes, converging toward the activation of inflammatory processes, oxidative stress, remodeling of cellular function and morphology, and disturbance of metabolic pathways. The growing interest in the characterization of protein post-translational modifications and the importance of handling large datasets using a systems biology approach are also discussed.

scholarly journals Mechanistic Insight of Na/K-ATPase Signaling and HO-1 into Models of Obesity and Nonalcoholic Steatohepatitis

2019 ◽  
Vol 21 (1) ◽  
pp. 87 ◽  
Author(s):  
Rebecca Pratt ◽  
Hari Vishal Lakhani ◽  
Mishghan Zehra ◽  
Rutmann Desauguste ◽  
Sneha S. Pillai ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nonalcoholic Steatohepatitis ◽  
Redox Regulation ◽  
Molecular Mechanisms ◽  
Antioxidant Properties ◽  
Molecular Targets ◽  
Heme Oxygenase 1 ◽  
Src Signaling ◽  
Amplification Loop ◽  
Pathophysiological Condition

Obesity is a multifaceted pathophysiological condition that has been associated with lipid accumulation, adipocyte dysfunction, impaired mitochondrial biogenesis and an altered metabolic profile. Redox imbalance and excessive release of inflammatory mediators have been intricately linked in obesity-associated phenotypes. Hence, understanding the mechanisms of redox signaling pathways and molecular targets exacerbating oxidative stress is crucial in improving health outcomes. The activation of Na/K-ATPase/Src signaling, and its downstream pathways, by reactive oxygen species (ROS) has been recently implicated in obesity and subsequent nonalcoholic steatohepatitis (NASH), which causes further production of ROS creating an oxidant amplification loop. Apart from that, numerous studies have also characterized antioxidant properties of heme oxygenase 1 (HO-1), which is suppressed in an obese state. The induction of HO-1 restores cellular redox processes, which contributes to inhibition of the toxic milieu. The novelty of these independent mechanisms presents a unique opportunity to unravel their potential as molecular targets for redox regulation in obesity and NASH. The attenuation of oxidative stress, by understanding the underlying molecular mechanisms and associated mediators, with a targeted treatment modality may provide for improved therapeutic options to combat clinical disorders.

scholarly journals Which Therapy for Non-Type(T)2/T2-Low Asthma

2021 ◽  
Vol 12 (1) ◽  
pp. 10
Author(s):  
Fabio L. M. Ricciardolo ◽  
Vitina Carriero ◽  
Francesca Bertolini
Keyword(s):  
Molecular Mechanisms ◽  
Inhaled Corticosteroids ◽  
First Choice ◽  
Inflammatory Processes ◽  
Muscarinic Drugs ◽  
Long Acting ◽  
Type 3

Currently, the asthmatic population is divided into Type 2-high and non-Type 2/Type 2-low asthmatics, with 50% of patients belonging to one of the two groups. Differently from T2-high, T2-low asthma has not been clearly defined yet, and the T2-low patients are identified on the basis of the absence or non-predominant expression of T2-high biomarkers. The information about the molecular mechanisms underpinning T2-low asthma is scarce, but researchers have recognized as T2-low endotypes type 1 and type 3 immune response, and remodeling events occurring without inflammatory processes. In addition, the lack of agreed biomarkers reprents a challenge for the research of an effective therapy. The first-choice medication is represented by inhaled corticosteroids despite a low efficacy is reported for/in T2-low patients. However, macrolides and long-acting anti-muscarinic drugs have been recognized as efficacious. In recent years, clinical trials targeting biomarkers playing key roles in T3 and T1 immune pathways, alarmins, and molecules involved in neutrophil recruitment have provided conflicting results probably misleading (or biased) in patients’ selection. However, further studies are warranted to achieve a precise characterization of T2-low asthma with the aim of defining a tailored therapy for each single asthmatic patient.

scholarly journals Multiple Biological Effects of an Iridoid Glucoside, Catalpol, and Its Underlying Molecular Mechanisms

Biomolecules ◽  
2019 ◽  
Vol 10 (1) ◽  
pp. 32 ◽  
Author(s):  
Subrat Kumar Bhattamisra ◽  
Kah Heng Yap ◽  
Vikram Rao ◽  
Hira Choudhury
Keyword(s):  
Molecular Mechanisms ◽  
Biological Effects ◽  
Antioxidant Properties ◽  
Experimental Studies ◽  
Extensive Literature ◽  
Rehmannia Glutinosa ◽  
Iridoid Glucoside ◽  
Anti Inflammatory

Catalpol, an iridoid glucoside, is widely distributed in many plant families and is primarily obtained from the root of Rehmannia glutinosa Libosch. Rehmannia glutinosa is a plant very commonly used in Chinese and Korean traditional medicine for various disorders, including diabetes mellitus, neuronal disorders, and inflammation. Catalpol has been studied extensively for its biological properties both in vitro and in vivo. This review aims to appraise the biological effects of catalpol and their underlying mechanisms. An extensive literature search was conducted using the keyword “Catalpol” in the public domains of Google scholar, PubMed, and Scifinder. Catalpol exhibits anti-diabetic, cardiovascular protective, neuroprotective, anticancer, hepatoprotective, anti-inflammatory, and anti-oxidant effects in experimental studies. Anti-inflammatory and antioxidant properties are mostly related for its biological effect. However, some specific mechanisms are also elucidated. Elevated serotonin and BDNF level by catalpol significantly protect against depression and neurodegeneration. Catalpol demonstrated an increased mitochondrial biogenesis and activation of PI3K/Akt pathway for insulin sensitizing effect. Further, its cardiovascular protective effect was linked to PI3K/Akt, apelin/APJ and Jak-Stat pathway. Catalpol produced a significant reduction in cell proliferation and an increase in apoptosis in different cancer conditions. Overall, catalpol demonstrated multiple biological effects due to its numerous mechanisms including anti-inflammatory and antioxidant effects.

Inflammageing in the cardiovascular system: mechanisms, emerging targets, and novel therapeutic strategies

2020 ◽  
Vol 134 (17) ◽  
pp. 2243-2262
Author(s):  
Danlin Liu ◽  
Gavin Richardson ◽  
Fehmi M. Benli ◽  
Catherine Park ◽  
João V. de Souza ◽  
...  
Keyword(s):  
Cardiovascular Diseases ◽  
Cardiovascular System ◽  
Nlrp3 Inflammasome ◽  
Molecular Mechanisms ◽  
Molecular Targets ◽  
Therapeutic Interventions ◽  
Low Grade ◽  
Cardiovascular Research ◽  
Inflammatory Processes ◽  
Ach Receptors

Abstract In the elderly population, pathological inflammation has been associated with ageing-associated diseases. The term ‘inflammageing’, which was used for the first time by Franceschi and co-workers in 2000, is associated with the chronic, low-grade, subclinical inflammatory processes coupled to biological ageing. The source of these inflammatory processes is debated. The senescence-associated secretory phenotype (SASP) has been proposed as the main origin of inflammageing. The SASP is characterised by the release of inflammatory cytokines, elevated activation of the NLRP3 inflammasome, altered regulation of acetylcholine (ACh) nicotinic receptors, and abnormal NAD+ metabolism. Therefore, SASP may be ‘druggable’ by small molecule therapeutics targeting those emerging molecular targets. It has been shown that inflammageing is a hallmark of various cardiovascular diseases, including atherosclerosis, hypertension, and adverse cardiac remodelling. Therefore, the pathomechanism involving SASP activation via the NLRP3 inflammasome; modulation of NLRP3 via α7 nicotinic ACh receptors; and modulation by senolytics targeting other proteins have gained a lot of interest within cardiovascular research and drug development communities. In this review, which offers a unique view from both clinical and preclinical target-based drug discovery perspectives, we have focused on cardiovascular inflammageing and its molecular mechanisms. We have outlined the mechanistic links between inflammageing, SASP, interleukin (IL)-1β, NLRP3 inflammasome, nicotinic ACh receptors, and molecular targets of senolytic drugs in the context of cardiovascular diseases. We have addressed the ‘druggability’ of NLRP3 and nicotinic α7 receptors by small molecules, as these proteins represent novel and exciting targets for therapeutic interventions targeting inflammageing in the cardiovascular system and beyond.

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