Histidine-rich calcium-binding protein: a molecular integrator of cardiac excitation-contraction coupling.

During mammalian cardiomyocyte excitation-contraction coupling, Ca2+ influx through voltage-gated Ca2+ channels triggers Ca2+ release from the sarcoplasmic reticulum (SR) through ryanodine receptor channels. This Ca2+-induced Ca2+ release mechanism controls cardiomyocyte contraction and is exquisitely regulated by SR Ca2+ levels. The histidine-rich calcium-binding protein (HRC) and its aspartic acid-rich paralogue aspolin are high-capacity, low-affinity Ca2+-binding proteins.

Impaired Upper Airway Muscle Function with Excessive or Deficient Dietary Intake of Selenium in Rats.

Obstructive sleep apnoea (OSA) involves impaired upper airway muscle function and is linked to several pathologies including systemic hypertension, daytime somnolence and cognitive decline. Selenium is an essential micronutrient that exerts many of its effects through selenoproteins. Evidence indicates that either deficient or excessive dietary selenium intake can result in impaired muscle function, termed nutritional myopathy.

Non-inositol 1,4,5-trisphosphate (IP) receptor IP-binding proteins.

Conventionally, myo-D-inositol 1, 4,5-trisphosphate (IP) is thought to exert its second messenger effects through the gating of IPR Ca release channels, located in Ca-storage organelles like the endoplasmic reticulum. However, there is considerable indirect evidence to support the concept that IP might interact with other, non-IPR proteins within cells. To explore this possibility further, the Protein Data Bank was searched using the term "IP3".

The synthetic TRPML1 agonist ML-SA1 rescues Alzheimer-related alterations of the endosomal-autophagic-lysosomal system.

Abnormalities in the endosomal-autophagic-lysosomal (EAL) system are an early event in Alzheimer's disease (AD) pathogenesis. However, the mechanisms underlying these abnormalities are unclear. The transient receptor potential channel mucolipin 1(TRPML1, also known as MCOLN1), a vital endosomal-lysosomal Ca2+ channel whose loss of function leads to neurodegeneration, has not been investigated with respect to EAL pathogenesis in late-onset AD (LOAD).

Implication of Oxysterols in Infectious and Non-Communicable Inflammatory Diseases.

Oxysterols, derived from cholesterol oxidation, are formed either by autoxidation, via enzymes, or by both processes [...

-D-inositol Trisphosphate Signalling in Oomycetes.

Oomycetes are pathogens of plants and animals, which cause billions of dollars of global losses to the agriculture, aquaculture and forestry sectors each year. These organisms superficially resemble fungi, with an archetype being , the cause of late blight of tomatoes and potatoes. Comparison of the physiology of oomycetes with that of other organisms, such as plants and animals, may provide new routes to selectively combat these pathogens.

Impact of cancer cachexia on respiratory muscle function and the therapeutic potential of exercise.

Cancer cachexia is defined as a multi-factorial syndrome characterised by an ongoing loss of skeletal muscle mass and progressive functional impairment, estimated to affect 50-80% of patients and responsible for 20% of cancer deaths. Elevations in the morbidity and mortality rates of cachectic cancer patients has been linked to respiratory failure due to atrophy and dysfunction of the ventilatory muscles. Despite this, there is a distinct scarcity of research investigating the structural and functional condition of the respiratory musculature in cancer, with the majority of studies exclusively focusing on limb muscle.

Evolution of the cardiac dyad.

Cardiac dyads are the site of communication between the sarcoplasmic reticulum (SR) and infoldings of the sarcolemma called transverse-tubules (TT). During heart excitation-contraction coupling, Ca-influx through L-type Ca channels in the TT is amplified by release of Ca-from the SR via type 2 ryanodine receptors, activating the contractile apparatus. Key proteins involved in cardiac dyad function are bridging integrator 1 (BIN1), junctophilin 2 and caveolin 3.

Compliance of the fish outflow tract is altered by thermal acclimation through connective tissue remodelling.

To protect the gill capillaries from high systolic pulse pressure, the fish heart contains a compliant non-contractile chamber called the bulbus arteriosus which is part of the outflow tract (OFT) which extends from the ventricle to the ventral aorta. Thermal acclimation alters the form and function of the fish atria and ventricle to ensure appropriate cardiac output at different temperatures, but its impact on the OFT is unknown. Here we used pressure-volume curves to demonstrate remodelling of passive stiffness in the rainbow trout () bulbus arteriosus following more than eight weeks of thermal acclimation to 5, 10 and 18°C.

Ryanodine receptor calcium release channels in trophoblasts and their role in cell migration.

Trophoblasts are specialized epithelial cells of the placenta that are involved in invasion, communication and the exchange of materials between the mother and fetus. Cytoplasmic Ca ([Ca]) plays critical roles in regulating such processes in other cell types, but relatively little is known about the mechanisms that control this second messenger in trophoblasts. In the current study, the presence of RyRs and their accessory proteins in placental tissues and in the BeWo choriocarcinoma, a model trophoblast cell-line, were examined using immunohistochemistry and Western immunoblotting.

Polyphenols of the Mediterranean Diet and Their Metabolites in the Prevention of Colorectal Cancer.

The Mediterranean diet is a central element of a healthy lifestyle, where polyphenols play a key role due to their anti-oxidant properties, and for some of them, as nutripharmacological compounds capable of preventing a number of diseases, including cancer. Due to the high prevalence of intestinal cancer (ranking second in causing morbidity and mortality), this review is focused on the beneficial effects of selected dietary phytophenols, largely present in Mediterranean cooking: apigenin, curcumin, epigallocatechin gallate, quercetin-rutine, and resveratrol. The role of the Mediterranean diet in the prevention of colorectal cancer and future perspectives are discussed in terms of food polyphenol content, the effectiveness, the plasma level, and the importance of other factors, such as the polyphenol metabolites and the influence of the microbiome.

7-Ketocholesterol: Effects on viral infections and hypothetical contribution in COVID-19.

7-Ketocholesterol, which is one of the earliest cholesterol oxidization products identified, is essentially formed by the auto-oxidation of cholesterol. In the body, 7-ketocholesterol is both provided by food and produced endogenously. This pro-oxidant and pro-inflammatory molecule, which can activate apoptosis and autophagy at high concentrations, is an abundant component of oxidized Low Density Lipoproteins.

Alterations in the Ca toolkit in oesophageal adenocarcinoma.

Aim: To investigate alterations in transcription of genes, encoding Ca toolkit proteins, in oesophageal adenocarcinoma (OAC) and to assess associations between gene expression, tumor grade, nodal-metastatic stage, and patient survival.

Methods: The expression of 275 transcripts, encoding components of the Ca toolkit, was analyzed in two OAC datasets: the Cancer Genome Atlas [via the University of Alabama Cancer (UALCAN) portal] and the oesophageal-cancer, clinical, and molecular stratification [Oesophageal Cancer Clinical and Molecular Stratification (OCCAMS)] dataset. Effects of differential expression of these genes on patient survival were determined using Kaplan-Meier log-rank tests.

Prevention by Dietary Polyphenols (Resveratrol, Quercetin, Apigenin) Against 7-Ketocholesterol-Induced Oxiapoptophagy in Neuronal N2a Cells: Potential Interest for the Treatment of Neurodegenerative and Age-Related Diseases.

The Mediterranean diet is associated with health benefits due to bioactive compounds such as polyphenols. The biological activities of three polyphenols (quercetin (QCT), resveratrol (RSV), apigenin (API)) were evaluated in mouse neuronal N2a cells in the presence of 7-ketocholesterol (7KC), a major cholesterol oxidation product increased in patients with age-related diseases, including neurodegenerative disorders. In N2a cells, 7KC (50 µM; 48 h) induces cytotoxic effects characterized by an induction of cell death.

Polycystic Kidney Disease Ryanodine Receptor Domain (PKDRR) Proteins in Oomycetes.

In eukaryotes, two sources of Ca are accessed to allow rapid changes in the cytosolic levels of this second messenger: the extracellular medium and intracellular Ca stores, such as the endoplasmic reticulum. One class of channel that permits Ca entry is the transient receptor potential (TRP) superfamily, including the polycystic kidney disease (PKD) proteins, or polycystins. Channels that release Ca from intracellular stores include the inositol 1,4,5-trisphosphate/ryanodine receptor (ITPR/RyR) superfamily.

Synthesis and Evaluation of Novel Ellipticines and Derivatives as Inhibitors of .

The pathogen is responsible for worldwide catastrophic crop damage and discovery of new inhibitors of this organism is of paramount agricultural and industrial importance. Current strategies for crop treatment are inadequate with limitations of efficacy and market alternatives. Ellipticines have recently been reported to have fungicidal properties and have been assessed against growth with promising results.

Inhibitory Properties of Aldehydes and Related Compounds against -Identification of a New Lead.

The pathogen is responsible for catastrophic crop damage on a global scale which totals billions of euros annually. The discovery of new inhibitors of this organism is of paramount agricultural importance and of critical relevance to food security. Current strategies for crop treatment are inadequate with the emergence of resistant strains and problematic toxicity.

Oxiapoptophagy: A type of cell death induced by some oxysterols.

Oxysterols are oxidized forms of cholesterol generated from cholesterol by auto-oxidation, enzymatic processes, or both. Some of them (7-ketocholesterol, 7β-hydroxycholesterol and 24(S)-hydroxycholesterol), when used at cytotoxic concentrations on different cell types from different species (mesenchymal bone marrow cells, monocytic cells and nerve cells), induce a type of cell death associated with OXIdative stress and several characteristics of APOPTOsis and autoPHAGY, defined as oxiapoptophagy. Oxidative stress is associated with overproduction of ROS, increased antioxidant enzyme activities, lipid peroxidation and protein carbonylation.

Evolution of Excitation-Contraction Coupling.

In mammalian cardiomyocytes, Ca influx through L-type voltage-gated Ca channels (VGCCs) is amplified by release of Ca via type 2 ryanodine receptors (RyR2) in the sarcoplasmic reticulum (SR): a process termed Ca-induced Ca-release (CICR). In mammalian skeletal muscles, VGCCs play a distinct role as voltage-sensors, physically interacting with RyR1 channels to initiate Ca release in a mechanism termed depolarisation-induced Ca-release (DICR). In the current study, we surveyed the genomes of animals and their close relatives, to explore the evolutionary history of genes encoding three proteins pivotal for ECC: L-type VGCCs; RyRs; and a protein family that anchors intracellular organelles to plasma membranes, namely junctophilins (JPHs).

7-Ketocholesterol and 7β-hydroxycholesterol: In vitro and animal models used to characterize their activities and to identify molecules preventing their toxicity.

Oxysterols are molecules derived by the oxidation of cholesterol and can be formed either by auto-oxidation, enzymatically or by both processes. Among the oxysterols formed by auto-oxidation, 7-ketocholesterol and 7β-hydroxycholesterol are the main forms generated. These oxysterols, formed endogenously and brought in large quantities by certain foods, have major cytotoxic properties.

Processive Recoding and Metazoan Evolution of Selenoprotein P: Up to 132 UGAs in Molluscs.

Selenoproteins typically contain a single selenocysteine, the 21st amino acid, encoded by a context-redefined UGA. However, human selenoprotein P (SelenoP) has a redox-functioning selenocysteine in its N-terminal domain and nine selenium transporter-functioning selenocysteines in its C-terminal domain. Here we show that diverse SelenoP genes are present across metazoa with highly variable numbers of Sec-UGAs, ranging from a single UGA in certain insects, to 9 in common spider, and up to 132 in bivalve molluscs.

Dimethyl fumarate and monomethyl fumarate attenuate oxidative stress and mitochondrial alterations leading to oxiapoptophagy in 158N murine oligodendrocytes treated with 7β-hydroxycholesterol.

Oxidative stress and mitochondrial dysfunction contribute to the pathogenesis of neurodegenerative diseases and favor lipid peroxidation, leading to increased levels of 7β-hydroxycholesterol (7β-OHC) which induces oxiapoptophagy (OXIdative stress, APOPTOsis, autoPHAGY). The cytoprotective effects of dimethylfumarate (DMF), used in the treatment of relapsing remitting multiple sclerosis and of monomethylfumarate (MMF), its main metabolite, were evaluated on murine oligodendrocytes 158 N exposed to 7β-OHC (50 μM, 24 h) with or without DMF or MMF (25 μM). The activity of 7β-OHC in the presence or absence DMF or MMF was evaluated on several parameters: cell adhesion; plasma membrane integrity measured with propidium iodide (PI), trypan blue and fluoresceine diacetate (FDA) assays; LDH activity; antioxidant enzyme activities (superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx)); generation of lipid peroxidation products (malondialdehyde (MDA), conjugated dienes (CDs)) and protein oxidation products (carbonylated proteins (CPs)); reactive oxygen species (ROS) overproduction conducted with DHE and DHR123.

Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities.

Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined.

Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO).

Biotin attenuation of oxidative stress, mitochondrial dysfunction, lipid metabolism alteration and 7β-hydroxycholesterol-induced cell death in 158N murine oligodendrocytes.

Mitochondrial dysfunction and oxidative stress are involved in neurodegenerative diseases associated with an enhancement of lipid peroxidation products such as 7β-hydroxycholesterol (7β-OHC). It is, therefore, important to study the ability of 7β-OHC to trigger mitochondrial defects, oxidative stress, metabolic dysfunctions and cell death, which are hallmarks of neurodegeneration, and to identify cytoprotective molecules. The effects of biotin were evaluated on 158N murine oligodendrocytes, which are myelin synthesizing cells, exposed to 7β-OHC (50 µM) with or without biotin (10 and 100 nM) or α-tocopherol (positive control of cytoprotection).

Calcium Signaling in Oomycetes: An Evolutionary Perspective.

Oomycetes are a family of eukaryotic microbes that superficially resemble fungi, but which are phylogenetically distinct from them. These organisms cause major global economic losses to agriculture and fisheries, with representative pathogens being Phytophthora infestans, the cause of late potato blight and Saprolegnia diclina, the instigator of "cotton molds" in fish. As in all eukaryotes, cytoplasmic Ca(2+) is a key second messenger in oomycetes, regulating life-cycle transitions, controlling motility and chemotaxis and, in excess, leading to cell-death.