Selenium and Health: An Update on the Situation in the Middle East and North Africa.

Selenium (Se) is an important trace element that should be present in the diet of all age groups to provide an adequate intake. Se is incorporated in 25 known selenoproteins, which mediate the biological effects of Se including, immune response regulation, maintenance of thyroid function, antioxidant defense, and anti-inflammatory actions. A balanced intake of Se is critical to achieve health benefits because depending on its status, Se has been found to play physiological roles or contribute to the pathophysiology of various diseases including, neurodegenerative diseases, diabetes, cancer, and cardiovascular disorders. Se status and intake are very important to be known for a specific population as the levels of Se are highly variable among different populations and regions. In the Middle East and North African (MENA) region, very little is known about the status of Se. Studies available show that Se status is widely variable with some countries being deficient, some over sufficient, and some sufficient. This variability was apparent even within the same country between regions. In this review, we summarized the key roles of Se in health and disease and discussed the available data on Se status and intake among countries of the MENA region

E007 Differential effects of microparticles from human apoptotic T lymphocytes and from human apoptotic monocytes in endothelial cells

During cell activation or apoptosis, cells release vesicles, also called microparticles (MPs) from the plasma membrane. Since composition of MPs is dependent on cell origin and the type of stimulation, we compared the effects of MPs generated from both apoptotic T lymphocytes and apoptotic monocytes on endothelial function with respect to both nitric oxide (NO) pathway and reactive oxygen species (ROS). MPs were produced by treatment of either human T lymphocytes with the apoptotic agent actinomycin D or human monocytic cell line THP-1 with the apoptotic agent, the etoposide VP-16. Human Eahy 926 endothelial cells were incubated with 10μg/ml MPs for 24h. Apoptotic MPs from human T lymphocytes decreased NO production that was associated with overexpression and phosphorylation of endothelial NOsynthase (eNOS). Also, T lymphocytes MPs enhanced expression of caveolin-1 and decreased its phosphorylation. T lymphocytes MPs enhanced ROS by a mechanism sensitive to xanthine oxidase and P-IkappaBalpha inhibitors. PI3-kinase inhibition reduced the effects of T lymphocytes MPs on eNOS, but not on caveolin-1, whereas it enhanced the effects of MPs on ROS production. Inhibition of MEK reversed eNOS phosphorylation but it had no effect on ROS production induced by T lymphocytes MPs. By contrast, apoptotic MPs from human monocytes increased both NO production and in much less extent ROS. These effects were associated with a decrease of caveolin-1 expression and increased its phosphorylation, without affecting eNOS expression and phosphorylation. The inhibitor of the PI-3kinase, LY294002, reversed the effects of monocyte MPs on caveolin-1 expression but not on its phosphorylation. The MEK1/2 inhibitor, U0126, reversed the decrease of caveolin-1 expression induced by MPs from monocytes. Interestingly, U0126 potentiated ROS production induced by monocyte MPs. Whereas in vivo injection of T lymphocytes MPs in mice impaired endothelial function, apoptotic MPs from human monocytes did not affect endothelium-dependent relaxation. In addition, monocyte MPs were able to promote in vitro angiogenesis. In summary, these results highlight differential effects of apoptotic MPs from different origins by activating diverse multiple pathways related to NO and ROS productions

Differential modulation of oxidative and nitrosative stress pathways by red wine polyphenols, ProvinolsTM, in tissues from Zucker fatty rats (fa/fa).

Date du colloque : 2009National audienc

Microparticles as Biomarkers of Vascular Dysfunction in Metabolic Syndrome and its Individual Components

Heterogeneous in size (0.1-1 µm), microparticles are small membrane vesicles released from activated and/or apoptotic cells. Although described since 1967 by Wolf, it is only since the 1990’s that microparticles have been considered as biomarkers as well as potential mediators of biological messages between cells by acting as paracrine and endocrine vectors. Detection of microparticles has been performed in biological fluids (blood, synovial fluid, saliva for instance) and some solid tissues but also from the culture medium. Levels of circulating microparticles are enhanced in a large number of pathological states including cardiovascular and metabolic disorders associated with insulin resistance and this has been linked to deleterious effects on cells from the vascular wall, mainly, endothelial cells. This review highlights the increasing impact of microparticles in major cardiovascular pathological situations associated with metabolic derangements

Microparticles from patients with metabolic syndrome induce vascular hypo-reactivity via Fas/Fas-ligand pathway in mice

Peer reviewedPublisher PD

Myeloid-cell protein tyrosine phosphatase-1B deficiency in mice protects against high-fat diet and lipopolysaccharide-induced inflammation, hyperinsulinemia, and endotoxemia through an IL-10 STAT3-dependent mechanism.

Protein tyrosine phosphatase-1B (PTP1B) negatively regulates insulin and leptin signaling, rendering it an attractive drug target for treatment of obesity-induced insulin resistance. However, some studies suggest caution when targeting macrophage PTP1B, due to its potential anti-inflammatory role. We assessed the role of macrophage PTP1B in inflammation and whole-body metabolism using myeloid-cell (LysM) PTP1B knockout mice (LysM PTP1B). LysM PTP1B mice were protected against lipopolysaccharide (LPS)-induced endotoxemia and hepatic damage associated with decreased proinflammatory cytokine secretion in vivo. In vitro, LPS-treated LysM PTP1B bone marrow-derived macrophages (BMDMs) displayed increased interleukin (IL)-10 mRNA expression, with a concomitant decrease in TNF-α mRNA levels. These anti-inflammatory effects were associated with increased LPS- and IL-10-induced STAT3 phosphorylation in LysM PTP1B BMDMs. Chronic inflammation induced by high-fat (HF) feeding led to equally beneficial effects of macrophage PTP1B deficiency; LysM PTP1B mice exhibited improved glucose and insulin tolerance, protection against LPS-induced hyperinsulinemia, decreased macrophage infiltration into adipose tissue, and decreased liver damage. HF-fed LysM PTP1B mice had increased basal and LPS-induced IL-10 levels, associated with elevated STAT3 phosphorylation in splenic cells, IL-10 mRNA expression, and expansion of cells expressing myeloid markers. These increased IL-10 levels negatively correlated with circulating insulin and alanine transferase levels. Our studies implicate myeloid PTP1B in negative regulation of STAT3/IL-10-mediated signaling, highlighting its inhibition as a potential anti-inflammatory and antidiabetic target in obesity

Microparticles from patients with metabolic syndrome induce in vivo endothelial dysfunction and vascular hypo-reactivity by increasing oxidative and nitrosative stresses in mouse aorta

National audienc