The European Cooperation in Science and Technology (COST) provides an ideal framework to establish multi-disciplinary research networks. COST Action BM1203 (EU-ROS) represents a consortium of researchers from different disciplines who are dedicated to providing new insights and tools for better understanding redox biology and medicine and, in the long run, to finding new therapeutic strategies to target dysregulated redox processes in various diseases. This report highlights the major achievements of EU-ROS as well as research updates and new perspectives arising from its members. The EU-ROS consortium comprised more than 140 active members who worked together for four years on the topics briefly described below. The formation of reactive oxygen and nitrogen species (RONS) is an established hallmark of our aerobic environment and metabolism but RONS also act as messengers via redox regulation of essential cellular processes. The fact that many diseases have been found to be associated with oxidative stress established the theory of oxidative stress as a trigger of diseases that can be corrected by antioxidant therapy. However, while experimental studies support this thesis, clinical studies still generate controversial results, due to complex pathophysiology of oxidative stress in humans. For future improvement of antioxidant therapy and better understanding of redox-associated disease progression detailed knowledge on the sources and targets of RONS formation and discrimination of their detrimental or beneficial roles is required. In order to advance this important area of biology and medicine, highly synergistic approaches combining a variety of diverse and contrasting disciplines are needed.
Nitrite may be a source for nitric oxide ( U NO), particularly in highly acidic environments, such as the stomach. Diet products contribute also with reductants that dramatically increase the production of U NO from nitrite. Red wine has been attributed health promoting properties largely on basis of the reductive antioxidant properties of its polyphenolic fraction. We show in vitro that wine, wine anthocyanin fraction and wine catechol (caffeic acid) dose-and pH-dependently promote the formation of U NO when mixed with nitrite, as measured electrochemically. The production of U NO promoted by wine from nitrite was substantiated in vivo in healthy volunteers by measuring U NO in the air expelled from the stomach, following consumption of wine, as measured by chemiluminescence. Mechanistically, the reaction involves the univalent reduction of nitrite, as suggested by the formation of U NO and by the appearance of EPR spectra assigned to wine phenolic radicals. Ascorbic and caffeic acids cooperate in the reduction of nitrite to U NO. Moreover, reduction of nitrite is critically dependent on the phenolic structure and nitro-derivatives of phenols are also formed, as suggested by caffeic acid UV spectral modifications. The reduction of nitrite may reveal previously unrecognized physiologic effects of red wine in connection with U NO bioactivity.
Glucose‐induced insulin release from single islets of Langerhans is pulsatile. We have investigated the correlation between changes in cytosolic free calcium concentration ([Ca2+]i) and oscillatory insulin secretion from single mouse islets, in particular examining the basis for differences in secretory responses to intermediate and high glucose concentrations. Insulin release was monitored in real time through the amperometric detection of the surrogate insulin marker 5‐hydroxytryptamine (5‐HT) via carbon fibre microelectrodes. The [Ca2+]i was simultaneously recorded by whole‐islet fura‐2 microfluorometry. In 82 % of the experiments, exposure to 11 mM glucose evoked regular high‐frequency (average, 3.4 min−1) synchronous oscillations in amperometric current and [Ca2+]i. In the remaining experiments (18 %), 11 mM glucose induced an oscillatory pattern consisting of high‐frequency [Ca2+]i oscillations that were superimposed on low‐frequency (average, 0.32 min−1) [Ca2+]i waves. Intermittent high‐frequency [Ca2+]i oscillations gave rise to a similar pattern of pulsatile 5‐HT release. Raising the glucose concentration from 11 to 20 mM increased the duration of the steady‐state [Ca2+]i oscillations without increasing their amplitude. In contrast, both the duration and amplitude of the associated 5‐HT transients were increased by glucose stimulation. The amount of 5‐HT released per secretion cycle was linearly related to the duration of the underlying [Ca2+]i oscillations in both 11 and 20 mM glucose. The slopes of the straight lines were identical, indicating that there is no significant difference between the ability of calcium oscillations to elicit 5‐HT/insulin release in 11 and 20 mM glucose. In situ 5‐HT microamperometry has the potential to resolve the high‐frequency oscillatory component of the second phase of glucose‐induced insulin secretion. This component appears to reflect primarily the duration of the underlying [Ca2+]i oscillations, suggesting that glucose metabolism and/or access to glucose metabolites is not rate limiting to fast pulsatile insulin release.
carbon fiber microelectrode ͉ NO diffusional spread ͉ hippocampus
The development of new therapeutic approaches, combining efficacy and safety against intestinal inflammation, notably inflammatory bowel disease (IBD), has emerged as an important goal due to the significant side effects and the lack of effectiveness of standard current therapies. Recently, several studies described the health-promoting effects of red wine, including anti-inflammatory properties, but the molecular mechanisms underlying its beneficial role remain largely unknown. Red wine is rich in phenolic compounds and it has been suggested that the positive effect of red wine intake might be attributed not only to the antioxidant properties of these compounds but also to the modulation of signalling cascades in connection with physiological and pathophysiological conditions such as inflammatory processes. This study assesses the potential anti-inflammatory action of a red wine extract (RWE) enriched in polyphenols in a cellular model of intestinal inflammation using cytokines-stimulated HT-29 colon epithelial cells. RWE suppressed cytokines-induced IκB degradation and interleukin-8 production in a dose-dependent manner. Coherently, key inflammatory mediators downstream NF-κB activation; notably cyclooxygenase-2 and inducible nitric oxide synthase were maintained at low levels by RWE in the presence of the cytokines. Additionally, RWE inhibited both the increase of nitric oxide derived from iNOS and of protein tyrosine nitration, a biomarker of nitrosative stress that typically requires the reaction of nitric oxide with the superoxide radical. Taken together, the anti-inflammatory action of RWE, mechanistically supported by the modulation of cascades orchestrated by NF-κB and involving nitric oxide, suggests that RWE (a readily straightforward preparation when compared with the purification of specific compounds) may represent a simple and inexpensive therapeutic strategy in the context of intestinal inflammation.
We have assessed the relative contribution of Ca2+ entry and Ca2+ release from internal stores to the [Ca2+]i transients evoked by purinergic receptor activation in bovine adrenal chromaffin cells. The [Ca2+]i was recorded from single cells using ratiometric fura-2 microfluorometry. Two discrete groups of ATP-sensitive cells could be distinguished on the basis of their relative capacity to respond to ATP in the virtual absence of extracellular Ca2+. One group of cells (group I) failed to respond to ATP in the absence of Ca2+, was completely insensitive to UTP, and displayed suramin-blockable [Ca2+]i transients when challenged with ATP in the presence of external Ca2+. ATP activated a prominent and rapidly inactivating Mn2+ influx pathway in group I cells, as assessed by monitoring Mn2+ quenching of fura-2 fluorescence. In contrast, a second group of ATP-sensitive cells (group II) exhibited pronounced [Ca2+]i rises when challenged with ATP and UTP in the absence of Ca2+ and was completely insensitive to suramin. ATP and UTP activated a delayed and less prominent Mn2+ influx pathway in group II cells. Contrary to the nicotinic receptor agonist DMPP, which evoked a preferential release of epinephrine, ATP evoked a preferential release of norepinephrine, and UTP had no effect on secretion. Suramin nearly suppressed ATP-evoked norepinephrine release. We conclude that chromaffin cells contain two distinct and cell-specific purinoceptor subtypes. Although some cells express a P2U-type purinoceptor coupled to Ca2+ release from internal stores and to the associated slow Ca2+ refilling mechanism, other cells express a suramin-sensitive and UTP-insensitive purinoceptor exclusively coupled to Ca2+ influx, probably an ATP-gated channel. It is suggested that the ATP-gated channel is preferentially localized to norepinephrine-secreting chromaffin cells and supports specifically hormone output from these cells. Thus, the biochemical pathways involved in the exocytotic release of the two major stress-related hormones appear to be regulated by distinct signaling systems.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.