Intracellular Ca2+ release through ryanodine receptors contributes to AMPA receptor-mediated mitochondrial dysfunction and ER stress in oligodendrocytes

Overactivation of ionotropic glutamate receptors in oligodendrocytes induces cytosolic Ca2+ overload and excitotoxic death, a process that contributes to demyelination and multiple sclerosis. Excitotoxic insults cause well-characterized mitochondrial alterations and endoplasmic reticulum (ER) dysfunction, which is not fully understood. In this study, we analyzed the contribution of ER-Ca2+ release through ryanodine receptors (RyRs) and inositol triphosphate receptors (IP(3)Rs) to excitotoxicity in oligodendrocytes in vitro. First, we observed that oligodendrocytes express all previously characterized RyRs and IP(3)Rs. Blockade of Ca2+-induced Ca2+ release by TMB-8 following alpha-amino-3-hydroxyl-5-methyl-4-isoxazole-propionate (AMPA) receptor-mediated insults attenuated both oligodendrocyte death and cytosolic Ca2+ overload. In turn, RyR inhibition by ryanodine reduced as well the Ca2+ overload whereas IP3R inhibition was ineffective. Furthermore, AMPA-triggered mitochondrial membrane depolarization, oxidative stress and activation of caspase-3, which in all instances was diminished by RyR inhibition. In addition, we observed that AMPA induced an ER stress response as revealed by alpha subunit of the eukaryotic initiation factor 2 alpha phosphorylation, overexpression of GRP chaperones and RyR-dependent cleavage of caspase-12. Finally, attenuating ER stress with salubrinal protected oligodendrocytes from AMPA excitotoxicity. Together, these results show that Ca2+ release through RyRs contributes to cytosolic Ca2+ overload, mitochondrial dysfunction, ER stress and cell death following AMPA receptor-mediated excitotoxicity in oligodendrocytes. Cell Death and Disease (2010) 1, e54; doi:10.1038/cddis.2010.31; published online 15 July 2010

The promoter of cell growth- and RNA protection-associated SND1 gene is activated by endoplasmic reticulum stress in human hepatoma cells

Background: Staphyloccocal nuclease domain-containing protein 1 (SND1) is involved in the regulation of gene expression and RNA protection. While numerous studies have established that SND1 protein expression is modulated by cellular stresses associated with tumor growth, hypoxia, inflammation, heat- shock and oxidative conditions, little is known about the factors responsible for SND1 expression. Here, we have approached this question by analyzing the transcriptional response of human SND1 gene to pharmacological endoplasmic reticulum (ER) stress in liver cancer cells. Results: We provide first evidence that SND1 promoter activity is increased in human liver cancer cells upon exposure to thapsigargin or tunicamycin or by ectopic expression of ATF6, a crucial transcription factor in the unfolded protein response triggered by ER stress. Deletion analysis of the 5'-flanking region of SND1 promoter identified maximal activation in fragment (-934, +221), which contains most of the predicted ER stress response elements in proximal promoter. Quantitative real- time PCR revealed a near 3 fold increase in SND1 mRNA expression by either of the stress- inducers; whereas SND1 protein was maximally upregulated (3.4-fold) in cells exposed to tunicamycin, a protein glycosylation inhibitor. Conclusion: Promoter activity of the cell growth- and RNA-protection associated SND1 gene is up-regulated by ER stress in human hepatoma cells.

An Embedded Stress Sensor for Concrete SHM Based on Amorphous Ferromagnetic Microwires

A new smart concrete aggregate design as a candidate for applications in structural health monitoring (SHM) of critical elements in civil infrastructure is proposed. The cement-based stress/strain sensor was developed by utilizing the stress/strain sensing properties of a magnetic microwire embedded in cement-based composite (MMCC). This is a contact-less type sensor that measures variations of magnetic properties resulting from stress variations. Sensors made of these materials can be designed to satisfy the specific demand for an economic way to monitor concrete infrastructure health. For this purpose, we embedded a thin magnetic microwire in the core of a cement-based cylinder, which was inserted into the concrete specimen under study as an extra aggregate. The experimental results show that the embedded MMCC sensor is capable of measuring internal compressive stress around the range of 1-30 MPa. Two stress sensing properties of the embedded sensor under uniaxial compression were studied: the peak amplitude and peak position of magnetic switching field. The sensitivity values for the amplitude and position within the measured range were 5 mV/MPa and 2.5 mu s/MPa, respectively.

Dendrorremediación: El uso de Betula alba para monitorizar y reducir el contenido de metales en suelos mineros.

[EN] The intense industrial activity that took place over the past century resulted in large contaminated áreas. This is an important risk to human health and environmental safety. Recent biotechnological techniques for bioremediation include phytoremediation, which uses plants to remove or stabilize contaminants in soils. In our study we choose birch (Betula alba) as the preferred species to remedy mining soils, due to it produces a large biomass and can accumulate high levels of toxic elements in its tissues. The aim of this study was (i) to determine the possibility of using this species in reforestation and/or remediation of mining soils (ii) to elucidate the potential of tocopherol levels as indicators of heavy metal pollution. Trees growing in mining soils with high concentrations of Zn, Cd and Pb were sampled and the metal content in various organs and in tree rings was analyzed. α-tocoferol levels were also analyzed as an indicator of stress. The results showed a different distribution of metals in plant tissues. Zn and Cd had a higher accumulation in leaves, whereas Pb was stored in the timber. In addition, the metal content in tree rings was higher in older rings, leading to a conclusion that older tissues present a detoxification strategy. Furthermore, we saw how the presence of α- tocoferol on branches can be an indicator of metal stress in plants and it can be also used as a monitoring factor.

Dietary animal and plant protein intakes and their associations with obesity and cardio-metabolic indicators in European adolescents: the HELENA cross-sectional study

Background: Previous studies suggest that dietary protein might play a beneficial role in combating obesity and its related chronic diseases. Total, animal and plant protein intakes and their associations with anthropometry and serum biomarkers in European adolescents using one standardised methodology across European countries are not well documented. Objectives: To evaluate total, animal and plant protein intakes in European adolescents stratified by gender and age, and to investigate their associations with cardio-metabolic indicators (anthropometry and biomarkers). Methods: The current analysis included 1804 randomly selected adolescents participating in the HELENA study (conducted in 2006-2007) aged 12.5-17.5 y (47% males) who completed two non-consecutive computerised 24-h dietary recalls. Associations between animal and plant protein intakes, and anthropometry and serum biomarkers were examined with General linear Model multivariate analysis. Results: Average total protein intake exceeded the recommendations of World Health Organization and European Food Safety Authority. Mean total protein intake was 96 g/d (59% derived from animal protein). Total, animal and plant protein intakes (g/d) were significantly lower in females than in males and total and plant protein intakes were lower in younger participants (12.5-14.9 y). Protein intake was significantly lower in underweight subjects and higher in obese ones; the direction of the relationship was reversed after adjustments for body weight (g/(kg.d)). The inverse association of plant protein intakes was stronger with BMI z-score and body fat percentage (BF%) compared to animal protein intakes. Additionally, BMI and BF% were positively associated with energy percentage of animal protein. Conclusions: This sample of European adolescents appeared to have adequate total protein intake. Our findings suggest that plant protein intakes may play a role in preventing obesity among European adolescents. Further longitudinal studies are needed to investigate the potential beneficial effects observed in this study in the prevention of obesity and related chronic diseases.