17 research outputs found
Double-edged sword behaviour of gallic acid and its interaction with peroxidases in human microvascular endothelial cell culture (HMEC-1). Antioxidant and pro-oxidant effects*
A previous report from our group had shown in vitro a
direct interaction between peroxidases and dietary antioxidants
at physiological concentrations, where in the
absence of H2O2, the antioxidants could serve as oxidizing
substrates for the peroxidases. However, the physiological
relevance of those findings had not been evaluated.
The main objective of this study was to determine
whether the oxidizing products produced in the interaction
between peroxidase and gallic acid at a physiological
concentration of 1 μM may promote cell death or
survival in a human microvascular endothelial cell line
(HMEC-1). Our findings suggested that gallic acid may
show a double-edged sword behaviour, since in the absence
of H2O2 it may have a pro-oxidant effect which
may promote cell injury (evidenced by LDH, Crystal Violet
and calcein AM viability/citotoxicity assays), while in
the presence of H2O2, gallic acid may act as an antioxidant
inhibiting oxidative species produced in the peroxidase
cycle of peroxidases. These observations were confirmed
with several oxidative stress biomarkers and the
evaluation of the activation of cell survival pathways like
AKT and MAPK/ERK.This study was supported by grants from the Spanish Ministry of Science and Innovation (CENIT METDEV- FUN) to M. Portero-Otín, the Spanish Instituto de Salud Carlos III (FIS PI081238) to J. Boada and (FIS PI081843) to M. Portero-Otin and by the COST action B35
Early and gender-specific differences in spinal cord mitochondrial function and oxidative stress markers in a mouse model of ALS
Introduction: Amyotrophic lateral sclerosis (ALS) is a motor neuron disease with a gender bias towards major
prevalence in male individuals. Several data suggest the involvement of oxidative stress and mitochondrial
dysfunction in its pathogenesis, though differences between genders have not been evaluated. For this reason, we
analysed features of mitochondrial oxidative metabolism, as well as mitochondrial chain complex enzyme activities
and protein expression, lipid profile, and protein oxidative stress markers, in the Cu,Zn superoxide dismutase with
the G93A mutation (hSOD1-G93A)- transgenic mice and Neuro2A(N2A) cells overexpressing hSOD1-G93A.
Results and Conclusions: Our results show that overexpression of hSOD1-G93A in transgenic mice decreased
efficiency of mitochondrial oxidative phosphorylation, located at complex I, revealing a temporal delay in females
with respect to males associated with a parallel increase in selected markers of protein oxidative damage. Further,
females exhibit a fatty acid profile with higher levels of docosahexaenoic acid at 30 days. Mechanistic studies
showed that hSOD1-G93A overexpression in N2A cells reduced complex I function, a defect prevented by 17β-
estradiol pretreatment. In conclusion, ALS-associated SOD1 mutation leads to delayed mitochondrial dysfunction in
female mice in comparison with males, in part attributable to the higher oestrogen levels of the former. This study
is important in the effort to further understanding of whether different degrees of spinal cord mitochondrial
dysfunction could be disease modifiers in ALS.
Keywords: Motor neuron, Complex I, Respirometry, Fatty acid composition, Oxidative damage, EstrogensThis study was funded by the Spanish Ministry of Health, Institute Carlos III: FIS grants PI14/00757, PI14/00328, PI 14/01115. Financed by the European Union, program European Regional Development Fund “A way to build Europe”. Supported by the Generalitat de Catalunya (2014SGR168 and predoctoral fellows for OR-N and PT), by FUNDELA (C100013), “RedELA Investigación” platform and by the Fundació Miquel Valls (Jack Van den Hoek donation for ALS research
Tor1, Sch9 and PKA downregulation in quiescence rely on Mtl1 to preserve mitochondrial integrity and cell survival
Here we show that Mtl1, member of the cell wall integrity pathway of Saccharomyces cerevisiae, plays a positive role in chronological life span (CLS). The absence of Mtl1 shortens CLS and causes impairment in the mitochondrial function. This is reflected in a descent in oxygen consumption during the postdiauxic state, an increase in the uncoupled respiration and mitochondrial membrane potential and also a descent in aconitase activity. We demonstrate that all these effects are a consequence of signalling defects suppressed by TOR1 (target of rapamycin) and SCH9 deletion and less efficiently by Protein kinase A (PKA)inactivation. Mtl1 also plays a role in the regulation of both Bcy1 stability and phosphorylation, mainly in response to glucose depletion. In postdiauxic phase and in conditions of glucose depletion, Mtl1 negatively regulates TOR1 function leading to Sch9 inactivation and Bcy1 phosphorylation converging in PKA inhibition. Slt2/Mpk1 kinase partially contributes to Bcy1 phosphorylation, although additional targets are not excluded. Mtl1 links mitochondrial dysfunction with TOR and PKA pathways in quiescence, glucose being the main signalling molecule
Do primary health centres and hospitals contribute equally towards achievement of the transversal clinical competencies of medical students? Performance on the Objective Structured Clinical Examination (OSCE) in competency acquisition
Objectives: The adaptation of the educational programmes of European faculties of medicine
to the European Higher Education Area guidelines has focused curricula design on competence acquisition. Competencies are defined as the achievements of a predetermined level of efficacy in real-world scenarios. Our objective was to assess whether performance on a common
competence evaluation test, the Objective Structured Clinical Examination (OSCE), resulted in different scores for second-year students after a practical medical training course took place in a primary health centre (PHC) or in a hospital.
Design: A descriptive study was conducted during the 2010---2014 academic year of the OSCE
test scores obtained by all second-year students.
Location: Faculty of Medicine at the University of Lleida (Catalonia, Spain).
Main measurements: We performed a correlation analysis between students who completed
their practical medical training at the PHC and hospitals utilising Student’s t-test for comparison
of means.
Results: 423 students who completed internships at the PHC and at hospitals obtained OSCE
mean scores of 7.32 (SD; IC) (0.82; 7.18---7.47) points and 7.17 (0.83; 6.07---7.26) points, respectively
(p = 0.07)
The Biological basis of the aging process
El procés biològic bàsic subjacent de l'envelliment va ésser
avançat per la teoria de l'envelliment basada en els radicals lliures
l'any 1954: la reacció dels radicals lliures actius, produïts fisiològicament
en l'organisme, amb els constituents cel·lulars
inicia els canvis associats a l'envelliment. La implicació dels radicals
lliures en l'envelliment està relacionada amb el seu paper
clau en l'origen i l'evolució de la vida. La informació disponible
avui en dia ens mostra que la composició específica de les macromolècules
cel·lulars (proteïnes, àcids nucleics, lípids i carbohidrats)
en les espècies animals longeves tenen intrínsicament
una resistència elevada a la modificació oxidativa, la qual cosa
probablement contribueix a la longevitat superior d'aquestes
espècies. Les espècies longeves també mostren unes taxes reduïdes
de producció de radicals lliures i de lesió oxidativa. D'altra
banda, la restricció dietària disminueix la producció de radicals
lliures i la lesió molecular oxidativa. Aquests canvis estan
directament associats a la reducció de la ingesta de proteïnes
dels animals sotmesos a restricció, que alhora sembla que són
deguts específicament a la reducció de la ingesta de metionina.
En aquesta revisió s'emfatitza que una taxa baixa de generació
de lesió endògena i una resistència intrínsecament elevada a la
modificació de les macromolècules cel·lulars són trets clau de la
longevitat de les espècies animals.The basic chemical process underlying aging was first put forward
by the free radical theory of aging in 1956; the reaction of
active free radicals (normally produced within an organism itself)
with cellular constituents initiates the changes associated
with aging. The involvement of free radicals in aging is related
to their key role in the origin and evolution of life. The specific
composition of tissue macromolecules (proteins, nucleic acids,
lipids and carbohydrates) in long-lived animal species gives
them an intrinsically high resistance to modification that probably
contributes to the superior longevity of these species.
Long-lived species also show low rates of reactive oxygen
species (ROS) generation and oxidative damage to their mitochondria.
Dietary restriction further decreases mitochondrial
ROS production and oxidative molecular damage due to the
decreased intake of dietary proteins. These effects of protein
restriction seem to be specifically due to the lowered methionine
intake of protein and dietary restricted animals. Both a low
rate of generation of endogenous damage and an intrinsically
high resistance to the modification of tissue macromolecules
are key traits of animal longevity