Role of mitochondrial raft-like microdomains in the regulation of cell apoptosis

Lipid rafts are envisaged as lateral assemblies of specific lipids and proteins that dissociate and associate rapidly and form functional clusters in cell membranes. These structural platforms are not confined to the plasma membrane; indeed lipid microdomains are similarly formed at subcellular organelles, which include endoplasmic reticulum, Golgi and mitochondria, named raft-like microdomains. In addition, some components of raft-like microdomains are present within ER-mitochondria associated membranes. This review is focused on the role of mitochondrial raft-like microdomains in the regulation of cell apoptosis, since these microdomains may represent preferential sites where key reactions take place, regulating mitochondria hyperpolarization, fission-associated changes, megapore formation and release of apoptogenic factors. These structural platforms appear to modulate cytoplasmic pathways switching cell fate towards cell survival or death. Main insights on this issue derive from some pathological conditions in which alterations of microdomains structure or function can lead to severe alterations of cell activity and life span. In the light of the role played by raft-like microdomains to integrate apoptotic signals and in regulating mitochondrial dynamics, it is conceivable that these membrane structures may play a role in the mitochondrial alterations observed in some of the most common human neurodegenerative diseases, such as Amyotrophic lateral sclerosis, Huntington's chorea and prion-related diseases. These findings introduce an additional task for identifying new molecular target(s) of pharmacological agents in these pathologies

Efficacy of essential oil mouthwash with and without alcohol: a 3-Day plaque accumulation model

<p>Abstract</p> <p>Background</p> <p>The aim of this study was to evaluate the antiplaque effect of a new alcohol free essential oil mouthwash with respect to a control of an essential oil with alcohol mouthwash, using an <it>in vivo </it>plaque regrowth model of 3-days.</p> <p>Methods</p> <p>The study was designed as a double-masked, randomized, crossover clinical trial, involving 30 volunteers to compare two different essential oil containing mouthwashes, during a 3-day plaque accumulation model. After receiving a thorough professional prophylaxis at the baseline, over the next 3-days each volunteer refrained from all oral hygiene measures and had two daily rinses with 20 ml of the test mouthwash (alcohol free essential oil) or the control mouthwash (essential oil with alcohol). At the end of the each experimental period, plaque was assessed and the panelists filled out a questionnaire. Each subject underwent a 14 days washout period and there was a second allocation.</p> <p>Results</p> <p>The essential oil mouthwash with ethanol shows a better inhibitory effect of plaque regrowth in 3-days than the mouthwash test with only essential oil in the whole mouth (plaque index = 2.18 against 2.46, respectively, p < 0.05); for the lower jaw (plaque index = 2.28 against 2.57, respectively, p < 0.05); for the upper jaw (plaque index = 2.08 against 2.35, respectively, p < 0.05); for the incisors (plaque index = 1.93 against 2.27, respectively, p < 0.05); and the canines (plaque index = 1.99 against 2.47, respectively, p < 0.05).</p> <p>Conclusion</p> <p>The essential oil containing mouthwash without alcohol seems to have a less inhibiting effect on the plaque regrowth than the traditional alcoholic solution.</p> <p>Trial Registration</p> <p>ClinicalTrials.gov <a href="http://www.clinicaltrials.gov/ct2/show/NCT01411618">NCT01411618</a></p

IL-15 Participates in the Respiratory Innate Immune Response to Influenza Virus Infection

Following influenza infection, natural killer (NK) cells function as interim effectors by suppressing viral replication until CD8 T cells are activated, proliferate, and are mobilized within the respiratory tract. Thus, NK cells are an important first line of defense against influenza virus. Here, in a murine model of influenza, we show that virally-induced IL-15 facilitates the trafficking of NK cells into the lung airways. Blocking IL-15 delays NK cell entry to the site of infection and results in a disregulated control of early viral replication. By the same principle, viral control by NK cells can be therapeutically enhanced via intranasal administration of exogenous IL-15 in the early days post influenza infection. In addition to controlling early viral replication, this IL-15-induced mobilization of NK cells to the lung airways has important downstream consequences on adaptive responses. Primarily, depletion of responding NK1.1+ NK cells is associated with reduced immigration of influenza-specific CD8 T cells to the site of infection. Together this work suggests that local deposits of IL-15 in the lung airways regulate the coordinated innate and adaptive immune responses to influenza infection and may represent an important point of immune intervention

FYVE-Dependent Endosomal Targeting of an Arrestin-Related Protein in Amoeba

International audienceBACKGROUND: Visual and β-arrestins are scaffolding proteins involved in the regulation of receptor-dependent intracellular signaling and their trafficking. The arrestin superfamilly includes several arrestin domain-containing proteins and the structurally related protein Vps26. In Dictyostelium discoideum, the arrestin-domain containing proteins form a family of six members, namely AdcA to -F. In contrast to canonical arrestins, Dictyostelium Adc proteins show a more complex architecture, as they possess, in addition to the arrestin core, other domains, such as C2, FYVE, LIM, MIT and SAM, which potentially mediate selective interactions with either lipids or proteins. METHODOLOGY AND PRINCIPAL FINDINGS: A detailed analysis of AdcA has been performed. AdcA extends on both sides of the arrestin core, in particular by a FYVE domain which mediates selective interactions with PI(3)P, as disclosed by intrinsic fluorescence measurements and lipid overlay assays. Localization studies showed an enrichment of tagged- and endogenous AdcA on the rim of early macropinosomes and phagosomes. This vesicular distribution relies on a functional FYVE domain. Our data also show that the arrestin core binds the ADP-ribosylation factor ArfA, the unique amoebal Arf member, in its GDP-bound conformation. SIGNIFICANCE: This work describes one of the 6 arrestin domain-containing proteins of Dictyostelium, a novel and atypical member of the arrestin clan. It provides the basis for a better understanding of arrestin-related protein involvement in trafficking processes and for further studies on the expanding roles of arrestins in eukaryotes

The effector T cell response to influenza infection

Influenza virus infection induces a potent initial innate immune response, which serves to limit the extent of viral replication and virus spread. However, efficient (and eventual) viral clearance within the respiratory tract requires the subsequent activation, rapid proliferation, recruitment, and expression of effector activities by the adaptive immune system, consisting of antibody producing B cells and influenza-specific T lymphocytes with diverse functions. The ensuing effector activities of these T lymphocytes ultimately determine (along with antibodies) the capacity of the host to eliminate the viruses and the extent of tissue damage. In this review, we describe this effector T cell response to influenza virus infection. Based on information largely obtained in experimental settings (i.e., murine models), we will illustrate the factors regulating the induction of adaptive immune T cell responses to influenza, the effector activities displayed by these activated T cells, the mechanisms underlying the expression of these effector mechanisms, and the control of the activation/differentiation of these T cells, in situ, in the infected lungs