Search results for "Ostas"
showing 10 items of 874 documents
Hsp60 in Skeletal Muscle Fiber Biogenesis and Homeostasis: From Physical Exercise to Skeletal Muscle Pathology
2018
Hsp60 is a molecular chaperone classically described as a mitochondrial protein with multiple roles in health and disease, participating to the maintenance of protein homeostasis. It is well known that skeletal muscle is a complex tissue, rich in proteins, that is, subjected to continuous rearrangements, and this homeostasis is affected by many different types of stimuli and stresses. The regular exercise induces specific histological and biochemical adaptations in skeletal muscle fibers, such as hypertrophy and an increase of mitochondria activity and oxidative capacity. The current literature is lacking in information regarding Hsp60 involvement in skeletal muscle fiber biogenesis and reg…
A Thermodynamic Model of Monovalent Cation Homeostasis in the Yeast Saccharomyces cerevisiae
2016
Cationic and heavy metal toxicity is involved in a substantial number of diseases in mammals and crop plants. Therefore, the understanding of tightly regulated transporter activities, as well as conceiving the interplay of regulatory mechanisms, is of substantial interest. A generalized thermodynamic description is developed for the complex interplay of the plasma membrane ion transporters, membrane potential and the consumption of energy for maintaining and restoring specific intracellular cation concentrations. This concept is applied to the homeostasis of cation concentrations in the yeast cells of S. cerevisiae. The thermodynamic approach allows to model passive ion fluxes driven by the…
Metal homeostasis regulators suppress FRDA phenotypes in a drosophila model of the disease
2016
Friedreich's ataxia (FRDA), the most commonly inherited ataxia in populations of European origin, is a neurodegenerative disorder caused by a decrease in frataxin levels. One of the hallmarks of the disease is the accumulation of iron in several tissues including the brain, and frataxin has been proposed to play a key role in iron homeostasis. We found that the levels of zinc, copper, manganese and aluminum were also increased in a Drosophila model of FRDA, and that copper and zinc chelation improve their impaired motor performance. By means of a candidate genetic screen, we identified that genes implicated in iron, zinc and copper transport and metal detoxification can restore frataxin def…
Copper transporter COPT5 participates in the crosstalk between vacuolar copper and iron pools mobilisation
2019
Copper (Cu) deficiency affects iron (Fe) homeostasis in several plant processes, including the increased Fe requirements due to cuproprotein substitutions for the corresponding Fe counterpart. Loss-of-function mutants from Arabidopsis thaliana high affinity copper transporter COPT5 and Fe transporters NATURAL RESISTANCE-ASSOCIATED MACROPHAGE PROTEIN 3/4 (NRAMP3 and NRAMP4) were used to study the interaction between metals internal pools. A physiological characterisation showed that the copt5 mutant is sensitive to Fe deficiency, and that nramp3nramp4 mutant growth was severely affected under limiting Cu. By a transcriptomic analysis, we observed that NRAMP4 expression was highly induced in …
Temperature increases, hypoxia, and changes in food availability affect immunological biomarkers in the marine mussel Mytilus galloprovincialis
2017
Temperature increases, hypoxia, and changes in food availability are predicted to occur in the future. There is growing concern for the health status of wild and farmed organisms, since environmental stressors alter organism functions, and elicit coordinated physiological responses for homeostasis. Mussels are good bioindicators of environmental conditions. Their ability to maintain unaltered immunosurveillance under adverse environmental conditions may enhance their survival capability. Few studies are currently concerned with the relationships and feedback among multiple stressors. Here, food concentration, temperature, and oxygenation treatments were evaluated for their effects on immune…
Impaired DNA demethylation of C/EBP sites causes premature aging
2018
Changes in DNA methylation are among the best-documented epigenetic alterations accompanying organismal aging. However, whether and how altered DNA methylation is causally involved in aging have remained elusive. GADD45α (growth arrest and DNA damage protein 45A) and ING1 (inhibitor of growth family member 1) are adapter proteins for site-specific demethylation by TET (ten-eleven translocation) methylcytosine dioxygenases. Here we show that Gadd45a/Ing1 double-knockout mice display segmental progeria and phenocopy impaired energy homeostasis and lipodystrophy characteristic of Cebp (CCAAT/enhancer-binding protein) mutants. Correspondingly, GADD45α occupies C/EBPβ/δ-dependent superenhancers …
Sterol 27-hydroxylase polymorphism significantly associates with shorter telomere, higher cardiovascular and type-2 diabetes risk in obese subjects
2018
Background/objectivesThe pathologic relationship linking obesity and lipid dismetabolism with earlier onset of aging-related disorders, including cardiovascular disease (CVD) and type-2 diabetes (T2D), is not fully elucidate. Chronic inflammatory state, in obese individuals, may accelerate cellular aging. However, leukocyte telomere length (LTL), the cellular biological aging indicator, is elusively linked with obesity. Recent studies indicate that sterol 27-hydroxylase (CYP27A1) is an emerging antiatherogenic enzyme, that, by converting extrahepatic cholesterol to 27-hydroxycholesterol, facilitates cholesterol removal via high-density lipoprotein-cholesterol (HDL-C). We tested the hypothes…
The endoplasmic reticulum unfolded protein response in neurodegenerative disorders and its potential therapeutic significance
2017
In eukaryotic cells, the endoplasmic reticulum (ER) is the cell compartment involved in secretory protein translocation and quality control of secretory protein folding. Different conditions can alter ER function, resulting in the accumulation of unfolded or misfolded proteins within the ER lumen. Such a condition, known as ER stress, elicits an integrated adaptive response known as the unfolded protein response (UPR) that aims to restore proteostasis within the secretory pathway. Conversely, in prolonged cell stress or insufficient adaptive response, UPR signaling causes cell death. ER dysfunctions are involved and contribute to neuronal degeneration in several human diseases, including Al…
Post-transcriptional, post-translational and pharmacological regulation of tissue factor pathway inhibitor.
2018
: Tissue factor (TF) pathway inhibitor (TFPI) is an endogenous natural anticoagulant that readily inhibits the extrinsic coagulation initiation complex (TF-FVIIa-Xa) and prothrombinase (FXa, FVa and calcium ions). Alternatively, spliced TFPI isoforms (α, β and δ) are expressed by vascular and extravascular cells and regulate thrombosis and haemostasis, as well as cell signalling functions of TF complexes via protease-activated receptors (PARs). Proteolysis of TFPI plays an important role in regulating physiological roles of the TF pathway in host defense and possibly haemostasis. Elimination of TFPI inhibition has therefore been proposed as an approach to improve haemostasis in haemophilia …
Breaking BAG: The Co-Chaperone BAG3 in Health and Disease.
2016
Human BAG ( B cl-2-associated a thano g ene) proteins form a family of antiapoptotic proteins that currently consists of six members (BAG1–6) all sharing the BAG protein domain from which the name arises. Via this domain, BAG proteins bind to the heat shock protein 70 (Hsp70), thereby acting as a co-chaperone regulating the activity of Hsp70. In addition to their antiapoptotic activity, all human BAG proteins have distinct functions in health and disease, and BAG3 in particular is the focus of many investigations. BAG3 has a modular protein domain composition offering the possibility for manifold interactions with other proteins. Various BAG3 functions are implicated in disorders including …