Muscle-specific miRNAs in plasma and skeletal muscle of patients with idiopathic inflammatory myopathy are modulated by disease and training.

Objectives: Objective of this work was to examine myomiR levels in plasma, skeletal muscle, and skeletal muscle cells of patients with idiopathic inflammatory myopathy (IIM), their interrelations with the disease-related clinical phenotypes and with the effects of the disease-modifying 6-month training-intervention.

Methods: Samples of vastus lateralis muscle (n = 12/13) and plasma (n = 20/21) were obtained from IIM patients and healthy controls, respectively. Muscle and plasma were obtained before and after a 6-month training-intervention in 7 patients.

MyomiRs in cultured muscle cells from patients with idiopathic inflammatory myopathy are modulated by disease but not by 6-month exercise training.

Objectives: Idiopathic inflammatory myopathies/IIM are associated with changes in muscle-specific microRNA/miR. Exercise improves muscle function and metabolism in parallel with changes in miR expression. We investigated the effects of disease and exercise on miRs in differentiated muscle cells/myotubes from IIM patients and controls.

Clusterin is upregulated in serum and muscle tissue in idiopathic inflammatory myopathies and associates with clinical disease activity and cytokine profile.

Objectives: The aim of this cross-sectional study was to explore the circulating and skeletal muscle expression of clusterin (CLU) in inflammatory myopathies (IIM) and its potential implication in pathogenetic mechanisms of the disease.

Methods: A total of 85 IIM patients and 86 healthy controls (HC) were recruited. In addition, 20 IIM patients and 21 HC underwent a muscle biopsy.

Altered dynamics of lipid metabolism in muscle cells from patients with idiopathic inflammatory myopathy is ameliorated by 6 months of training.

Key Points: Regular exercise improves muscle functional capacity and clinical state of patients with idiopathic inflammatory myopathy (IIM). In our study, we used an in vitro model of human primary muscle cell cultures, derived from IIM patients before and after a 6-month intensive supervised training intervention to assess the impact of disease and exercise on lipid metabolism dynamics. We provide evidence that muscle cells from IIM patients display altered dynamics of lipid metabolism and impaired adaptive response to saturated fatty acid load compared to healthy controls.

Alterations in activin A-myostatin-follistatin system associate with disease activity in inflammatory myopathies.

Objectives: The aim of this study was to investigate the systemic and skeletal muscle levels of atrophy-associated myokines in patients with idiopathic inflammatory myopathies (IIM) and their association with clinical characteristics of myositis.

Methods: A total of 94 IIM patients and 162 healthy controls were recruited. Of those, 20 IIM patients and 28 healthy controls underwent a muscle biopsy.

Red palm oil supplementation does not increase blood glucose or serum lipids levels in Wistar rats with different thyroid status.

Red palm oil (RPO) is a rich natural source of antioxidant vitamins, namely carotenes, tocopherols and tocotrienols. However, it contains approximately 50 % saturated fatty acids the regular consumption of which could negatively modify lipid profile. The aim of our study was to test whether 7 weeks of RPO supplementation (1 g/kg body weight/day) would affect blood glucose and lipid metabolism in adult male Wistar rats with altered thyroid status.

The influence of erythrocyte maturity on ion transport and membrane lipid composition in the rat.

Significant relationships between ion transport and membrane lipid composition (cholesterol, total phospholipids and sphingomyelins) were found in erythrocytes of salt hypertensive Dahl rats. In these animals mean cellular hemoglobin content correlated negatively with Na(+)-K(+) pump activity and Na(+) leak but positively with Na(+)-K(+) cotransport activity. Immature erythrocytes exhibit lower mean cellular hemoglobin content (MCHC) than mature ones.

NADPH oxidase activity and reactive oxygen species production in brain and kidney of adult male hypertensive Ren-2 transgenic rats.

Hypothalamic paraventricular nucleus (PVN) and rostral ventrolateral medulla (RVLM) play an important role in brain control of blood pressure (BP). One of the important mechanisms involved in the pathogenesis of hypertension is the elevation of reactive oxygen species (ROS) production by nicotine adenine dinucleotide phosphate (NADPH) oxidase. The aim of our present study was to investigate NADPH oxidase-mediated superoxide (O(2)(-)) production and to search for the signs of lipid peroxidation in hypothalamus and medulla oblongata as well as in renal medulla and cortex of hypertensive male rats transgenic for the murine Ren-2 renin gene (Ren-2 TGR) and their age-matched normotensive controls - Hannover Sprague Dawley rats (HanSD).

ROS production is increased in the kidney but not in the brain of Dahl rats with salt hypertension elicited in adulthood.

Enhanced production of superoxide radicals by nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase in the brain and/or kidney of salt hypertensive Dahl rats has been proposed to participate in the pathogenesis of this form of experimental hypertension. Most information was obtained in young Dahl salt-sensitive (DS) rats subjected to high salt intake prior to sexual maturation. Therefore, the aim of our study was to investigate whether salt hypertension induced in adult DS rats is also accompanied with a more pronounced oxidative stress in the brain or kidney as compared to Dahl salt-resistant (DR) controls.

Inhibition of mitochondrial glycerol-3-phosphate dehydrogenase by α-tocopheryl succinate.

α-Tocopheryl succinate (TOS), a redox-silent analogue of vitamin E, suppresses cell growth in a number of clinical and experimental cancers, inhibits mitochondrial succinate dehydrogenase (SDH) and activates reactive oxygen species (ROS) generation. The aim of this study was to test whether TOS also inhibits glycerol-3-phosphate dehydrogenase (mGPDH), another flavoprotein-dependent enzyme of the mitochondrial respiratory chain because there are differences between electron transfer pathway from SDH and mGPDH to coenzyme Q pool. For our experiments brown adipose tissue mitochondria with high expression of mGPDH were used.

N-3 polyunsaturated fatty acids supplementation does not affect changes of lipid metabolism induced in rats by altered thyroid status.

Epidemiological studies have demonstrated that n-3 polyunsaturated fatty acid (PUFA) consumption is associated with a reduced risk of atherosclerosis and hyperlipidemia. It is well known that lipid metabolism is also influenced by thyroid hormones. The aim of our study was to test whether n-3 PUFA supplementation (200 mg/kg of body weight/day for 6 weeks given intragastrically) would affect lipid metabolism in Lewis male rats with altered thyroid status.

Chronic antioxidant therapy lowers blood pressure in adult but not in young Dahl salt hypertensive rats: the role of sympathetic nervous system.

Aim: It is well-known that salt hypertension is associated with increased oxidative stress. Since the development of salt hypertension is age-dependent, we were interested whether young and adult salt hypertensive Dahl rats differ in oxidative stress level and/or in the effects of chronic antioxidant therapy on blood pressure (BP) level and on the participation of particular vasoconstrictor/vasodilator systems in BP maintenance.

Methods: Young (5-week-old) and adult (12-week-old) salt-sensitive (Dahl-S) male rats were fed high-salt diet (5% NaCl) and drank tempol solution (2 mm) for 5 weeks.

Hypoxia-induced lipid peroxidation in the brain during postnatal ontogenesis.

Reactive oxygen species (ROS) are common products of the physiological metabolic reactions, which are associated with cell signaling and with the pathogenesis of various nervous disorders. The brain tissue has the high rate of oxidative metabolic activity, high concentration of polyunsaturated fatty acids in membrane lipids, presence of iron ions and low capacity of antioxidant enzymes, which makes the brain very susceptible to ROS action and lipid peroxidation formation. Membranes of brain cortex show a higher production of thiobarbituric acid-reactive substances (TBARS) in prooxidant system (ADP.

Age-dependent salt hypertension in Dahl rats: fifty years of research.

Fifty years ago, Lewis K. Dahl has presented a new model of salt hypertension - salt-sensitive and salt-resistant Dahl rats. Twenty years later, John P.

Idebenone-induced recovery of glycerol-3-phosphate and succinate oxidation inhibited by digitonin.

Digitonin solubilizes mitochondrial membrane, breaks the integrity of the respiratory chain and releases two mobile redox-active components: coenzyme Q (CoQ) and cytochrome c (cyt c). In the present study we report the inhibition of glycerol-3-phosphate- and succinate-dependent oxygen consumption rates by digitonin treatment. Our results show that the inhibition of oxygen consumption rates is recovered by the addition of exogenous synthetic analog of CoQ idebenone (hydroxydecyl-ubiquinone; IDB) and cyt c.

Glycerol-3-phosphate dehydrogenase expression and oxygen consumption in liver mitochondria of female and male rats with chronic alteration of thyroid status.

In our chronic experiments (over several months), the activity and protein amount of glycerol-3-phosphate dehydrogenase (GPDH) in mitochondria isolated from the liver of adult male and female inbred Lewis strain euthyroid (EU), hyperthyroid (TH), and hypothyroid (HY) rats were analyzed by biochemical and Western blot methods. The TH status was induced by intraperitoneal injections of 3,3',5-triiodo- L-thyronine and the HY status with 0.05% solution of methimazole in drinking water.

Endothelial cells negatively modulate reactive oxygen species generation in vascular smooth muscle cells: role of thioredoxin.

In intact vessels, endothelial cells (ECs) and vascular smooth muscle cells (VSMCs) act as an integrated system, possibly through reactive oxygen species (ROS). Using a coculture system we tested whether ECs modulate VSMC redox status by regulating activity of NAD(P)H oxidase and antioxidants. VSMC production of O(2)(*-), H(2)O(2), and NO was assessed using fluoroprobes and amplex-red.

Reactive oxygen species, cell growth, cell cycle progression and vascular remodeling in hypertension.

Reactive oxygen species (ROS) include superoxide, hygrogen peroxide and hydroxyl radical. Under physiological conditions, all vascular cell types produce ROS in a controlled and regulated fashion, mainly through nonphagocyte NADPH oxidase. An imbalance between pro-oxidants and antioxidants results in oxidative stress.

Erythrocyte ion transport in rats subjected to acute and chronic hypobaric hypoxia.

Our study addresses selected parameters of rat erythrocyte ion transport (Na(+)-K(+) pump, Na(+)-K(+)-2Cl- cotransport, and passive cation fluxes) after acute or chronic hypoxia exposure. We did not find any significant change of ion transport after acute hypoxia. However, chronic hypoxia could modify ion transport because the affinity of Na(+)-K(+) pump for intracellular Na(+) seems to be decreased.

Activity of lactate dehydrogenase in serum and cerebral cortex of immature and mature rats after hypobaric hypoxia.

In our previous studies we have found both an increase of lipid peroxidation damage (expressed as levels of thiobarbituric acid-reactive substances) in brain and plasma lactate concentration in 21-day-old rats after a 30-min exposure to hypobaric hypoxia. Pretreatment of rats with L-carnitine decreased both parameters. The aim of our present study was to determine if the L-carnitine-dependent decrease of plasma lactate could be due to a modification of lactate dehydrogenase (LDH) activity.

Chronic N-acetylcysteine administration prevents development of hypertension in N(omega)-nitro-L-arginine methyl ester-treated rats: the role of reactive oxygen species.

The aim of this study was to evaluate the production of superoxide anions as well as their role in the induction and/or maintenance of high blood pressure in rats with N(omega)-nitro-L-arginine methyl ester (L-NAME)-induced hypertension. In the preventive study, we compared adult Wistar rats treated with L-NAME for 4 weeks with L-NAME-treated rats that were simultaneously given N-acetylcysteine (NAC) in their drinking water. Basal blood pressure, superoxide production, conjugated dienes concentration and NO synthase (NOS) activity were measured at the end of the experiment.

Relationships between membrane lipids and ion transport in red blood cells of Dahl rats.

Distinct changes of membrane lipid content could contribute to the abnormalities of ion transport that take part in the development of salt hypertension in Dahl rats. The relationships between lipid content and particular ion transport systems were studied in red blood cells (RBC) of Dahl rats kept on low- and high-salt diets for 5 weeks since weaning. Dahl salt-sensitive (SS/Jr) rats on high-salt diet had increased blood pressure, levels of plasma triacylglycerols and total plasma cholesterol compared to salt-resistant (SR/Jr) rats.

Developmental changes of erythrocyte catalase activity in rats exposed to acute hypoxia.

The erythrocytes represent an important source of antioxidant capacity of the blood. Catalase (EC 1.11.

Altered balance of vasoactive systems in experimental hypertension: the role of relative NO deficiency.

This review summarizes our findings concerning the altered balance of vasoactive systems (namely sympathetic nervous system and nitric oxide) in various forms of experimental hypertension--genetic hypertension (SHR, HTG rats), salt hypertension (Dahl rats) and NO-deficient hypertension (L-NAME-treated rats). An attempt is made to define relative NO deficiency (compared to the existing level of sympathetic vasoconstriction), to describe its possible causes and to evaluate particular indicators of its extent. A special attention is paid to reactive oxygen species, their interaction with NO metabolism, cell Ca2+ handling and blood pressure regulation.

Membrane ion transport in erythrocytes of salt hypertensive Dahl rats and their F2 hybrids: the importance of cholesterol.

The possible association of salt hypertension and altered lipid metabolism with abnormalities of particular systems transporting sodium and potassium has been studied in erythrocytes of Dahl rats and their F2 hybrids fed a high-salt diet since weaning. Our attention was paid to the Na(+)-K+ pump, Na(+)-K+ cotransport and especially to passive membrane permeability for Na+ and Rb+ (Na+ and Rb+ leak), because the Na+ leak was found to be dependent on the genotype, age and salt intake of Dahl rats, whereas the Rb+ leak was suggested to be a potential marker of salt sensitivity in Dahl and Sabra rats. Young male Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) rats kept on a low-salt (0.