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Methylglyoxal induces endothelial cell apoptosis and coronary microvascular dysfunction through regulating AR-cPLA2 signaling.

OBJECTIVE: Since diabetic patients with coronary microvascular dysfunction (CMD) exhibit high cardiac mortality and women have higher prevalence of non-obstructive coronary artery disease than men, we tried to expand the limited understanding about the etiology and the sex difference of diabetic CMD. APPROACH AND RESULTS: Accumulated methylglyoxal (MGO) due to diabetes promotes vascular damage and it was used for mimicking diabetic status. Flow cytometry analysis and isometric tension measurement were performed to evaluate coronary artery endothelial injury. MGO induced apoptosis of coronary

Molecular Features of CA-074 pH-Dependent Inhibition of Cathepsin B.

CA-074 is a selective inhibitor of cathepsin B, a lysosomal cysteine protease. CA-074 has been utilized in numerous studies to demonstrate the role of this protease in cellular and physiological functions. Cathepsin B in numerous human disease mechanisms involves its translocation from acidic lysosomes of pH 4.6 to neutral pH 7.2 of cellular locations, including the cytosol and extracellular environment. To gain in-depth knowledge of CA-074 inhibition under these different pH conditions, this study evaluated the molecular features, potency, and selectivity of CA-074 for cathepsin B inhibition …

Engineering Tropane Alkaloid Production Based on Metabolic Characterization of Ornithine Decarboxylase in Atropa belladonna.

Ornithine decarboxylase (ODC) plays an important role in various biological processes; however, its role in plant secondary metabolism, especially in the biosynthesis of tropane alkaloids (TAs) such as pharmaceutical hyoscyamine, anisodamine, and scopolamine, remains largely unknown. In this study, we characterized the physiological and metabolic functions of the ODC gene of Atropa belladonna (AbODC) and determined its role in TA production using metabolic engineering approaches. Feeding assays with enzyme inhibitors indicated that ODC, rather than arginine decarboxylase (ADC), plays a major r

The Effects of Androgens on T Cells: Clues to Female Predominance in Autoimmune Liver Diseases?

The immune system responds differently in women and in men. Generally speaking, adult females show stronger innate and adaptive immune responses than males. This results in lower risk of developing most of the infectious diseases and a better ability to clear viral infection in women (1-5). On the other hand, women are at increased risk of developing autoimmune diseases (AID) such as rheumatoid arthritis, multiple sclerosis (MS), systemic lupus erythematosus (SLE), Sjögren's syndrome, and the autoimmune liver diseases autoimmune hepatitis (AIH) and primary biliary cholangitis (PBC) (6). Factor

Usnic acid, a lichen secondary metabolite inhibits Group A Streptococcus biofilms.

Group A Streptococci (GAS) are involved in a number of life threatening diseases and biofilm formation by these pathogens are considered as an important virulence determinant as it mediates antibiotic resistance among them. In the present study, we have explored the ability of (+)-usnic acid, a lichen secondary metabolite, as an antibiofilm agent against four serotypes of Streptococcus pyogenes causing pharyngitis. Usnic acid inhibited the biofilms of M serotypes M56, st38, M89 efficiently and the biofilm of M74 to a lesser extent. Confocal imaging of the treated samples showed that usnic acid

[NESPRINS--nuclear envelope proteins ensuring integrity].

This review describes the nesprins (nuclear envelope spectrin-repeat proteins), which are recently discovered family of nuclear envelope proteins. These proteins play an important role in maintaining the cellular architecture and establish the link between the nucleus and other sub-cellular compartments. Many tissue-specific diseases including lipodystrophies, hearing loss, cardiac and skeletal myopathies are associated with nesprins mutations. These proteins comprise of multiple tissue specific isoforms which contain spectrin repeats providing interaction of nesprins with other nuclear membra

Role of extracellular calcium and mitochondrial oxygen species in psychosine-induced oligodendrocyte cell death.

Globoid cell leukodystrophy (GLD) is a metabolic disease caused by mutations in the galactocerebrosidase (GALC) gene. GALC is a lysosomal en … e human oligodendrocyte cell line MO3.13, we report that cell death by PSY is accompanied by robust cytosolic and mitochondrial calcium (Ca(2+)) elevations, and by mitochondrial reactive oxygen species (ROS) production. Importantly, we demonstrate that the reduction of extracellular calcium content by the chelating agent ethylenediaminetetraacetic acid ca …

Взрослый вирион вируса эктомелии, патогенного поксивируса, способен к внутригепическому распространению и может служить мишенью для замедленной терапии.

Ортопоксивирусы (OPV), которые включают в себя агент оспы (вирус вариолы), зоонотические обезьянопоксовые вирусы, вакцину и зоонотические виды вакцины и патогенный вирус эктомелии мыши (ECTV), образуют два типа инфекционных вирусных частиц: зрелый вирус (MV), который является цитосолическим, и вирус, покрытый покрытием (EV), который является внеклеточным. Считается, что МВ необходимы для вирусного проникновения в хозяин, в то время как ЭМ несут ответственность за распространение внутри носителя. После патовой инфекции мышей, подверженных риску заражения, ECTV распространяет лимфохематологию, п

Совпадение в аннотации оригинала
Orthopoxviruses (OPVs), which include the agent of smallpox (variola virus), the zoonotic monkeypox virus, the vaccine and zoonotic species vaccinia virus, and the mouse pathogen ectromelia virus (ECTV), form two types of infectious viral particles: the mature virus (MV), which is cytosolic, and the enveloped virus (EV), which is extracellular. It is believe…

Using Jensen's inequality to explain the role of regular calcium oscillations in protein activation.

Oscillations of cytosolic Ca(2 +) are very important for cellular signalling in excitable and non-excitable cells. The information of various extracellular stimuli is encoded into oscillating patterns of Ca(2 +) that subsequently lead to the activation of different Ca(2 +)-sensitive target proteins in the cell. The question remains, however, why this information is transmitted by means of an oscillating rather than a constant signal. Here we show that, in fact, Ca(2 +) oscillations can achieve a better activation of target proteins than a comparable constant signal with the same amount of Ca(2…

Association of SULT2A1 allelic variants with plasma adrenal androgens and prostate cancer in African American men.

Dehydroepiandrosterone (DHEA) sulfate which is present at micromolar levels in the plasma, can be desulfated to supply free DHEA for metabolism to androgens or estrogens in peripheral tissues. Human cytosolic sulfotransferase (SULT) 2A1 catalyzes DHEA sulfation in the adrenal cortex. Three SULT2A1 nonsynonymous coding single nucleotide polymorphisms (SNPs), identified only in African Americans (AA), are associated with decreased levels of activity and expression as compared to wild-type cDNA when expressed in COS cells. To test whether the SNPs are associated with decreased plasma androgens, 1…

Mechanisms of copper loading on the Schizosaccharomyces pombe copper amine oxidase 1 expressed in Saccharomyces cerevisiae.

Copper amine oxidases (CAOs) are found in almost every living kingdom. Although Saccharomyces cerevisiae is one of the few yeast species tha … n active CAO. Using a functional spao1(+)-GFP fusion allele, the SPAO1 protein was localized in the cytosol. Under copper-limiting conditions, yeast cells harbouring deletions of the MAC1, CTR1 and CTR3 genes were defective in amine oxidase activity. Likewise, atx1Delta null cells exhibited no CAO activity, while ccc2Delta mutant cells exhibited decreased …

Involvement of calcium mobilization from caffeine-sensitive stores in mechanically induced cell cycle arrest in the dinoflagellate Crypthecodinium cohnii.

Mechanical loads can profoundly alter cell growth and cell proliferation. The dinoflagellates are especially sensitive to mechanical stimulation. Many species will be arrested in cell cycle in response to turbulence or shear stress. We demonstrate here that mechanical shaking and caffeine, the ryanodine-receptor agonist, induced an elevation of cytosolic calcium in the dinoflagellate Crypthecodinium cohnii. Dantrolene, a ryanodine-receptor antagonist, dose-dependently inhibited both shaking-induced and caffeine-induced calcium release. Similar to the effect of mechanical shaking, caffeine alon…

Mg2+ dependence of halothane-induced Ca2+ release from the sarcoplasmic reticulum in rat skeletal muscle.

The effect of cytosolic Mg2+ on halothane-induced Ca2+ release from the sarcoplasmic reticulum (SR) was investigated in mechanically skinned fibres from the rat extensor digitorum longus (EDL) muscle. Preparations were perfused with solutions mimicking the intracellular milieu and changes in [Ca2+] were detected using Fura-2 fluorescence. In the presence of 1 mM Mg2+, brief (500 ms) applications of 40 mM halothane failed to induce Ca2+ release from the SR. However, Ca2+ release became detectable when [Mg2+] was reduced to 0.4 mM, and the amplitude of the response increased progressively as [Mg…

Mechanisms involved in the chemoprevention of flavonoids.

Flavonoids, widespread in edible plants, have been studied extensively for their anticarcinogenic properties. However, only few studies have been done with these constituents being administered by the dietary route. In our research, the effects of feeding rats with flavone, flavanone, tangeretin, and quercetin were investigated on two steps of aflatoxin B1 (AFB1)-induced hepatocarcinogenesis (initiation and promotion). Nonpolar flavonoids such as flavone, flavanone and tangeretin administered through the initiation period, decreased the number of -gamma-glutamyl transpeptidase-preneoplastic fo

Sub-second quenched-flow/X-ray microanalysis shows rapid Ca2+ mobilization from cortical stores paralleled by Ca2+ influx during synchronous exocytosis in Paramecium cells.

Though only actual local free Ca2+ concentrations, [Ca2+], rather than total Ca concentrations, [Ca], govern cellular responses, analysis of total calcium fluxes would be important to fully understand the very complex Ca2+ dynamics during cell stimulation. Using Paramecium cells we analyzed Ca2+ mobilization from cortical stores during synchronous (< or = 80 ms) exocytosis stimulation, by quenched-flow/cryofixation, freeze-substitution (modified for Ca retention) and X-ray microanalysis which registers total calcium concentrations, [Ca]. When the extracellular free calcium concentration, [Ca2+

The cardiac adrenergic system in ischaemia: differential role of acidosis and energy depletion.

OBJECTIVE: Acute myocardial ischaemia has been shown to modulate the beta-adrenergic system and to activate protein kinase C. The aim of this study was to investigate if two important components of ischaemia, i.e. energy depletion or acidosis, may contribute to these changes. METHODS: Isolated rat hearts were perfused either with anoxia (in the absence of oxygen) or with cyanide in the absence of glucose as models of energy depletion with a loss of high energy phosphates. Alternatively, isolated hearts were perfused with acidic modified Krebs-Henseleit solution to induce acidosis. RESULTS: E

Tumor-related selection of calcium signals in vasopressin-stimulated human adenomatous corticotrophs.

The action of arginine vasopressin (AVP) on cytosolic free calcium concentration ([Ca2+]i) was studied at the single-cell level in corticotrophs cultured from pituitary adenoma fragments removed from eight patients with Cushing's disease. AVP evoked distinct [Ca2+]i responses with regard to the tumor origin. In cells from two tumors, AVP consistently evoked a series of characteristic elevations of [Ca2+]i (transient pattern) that depended on Ca2+ entry. In cells from the other tumors, AVP triggered different patterns of [Ca2+]i rise, which consisted of low-amplitude slow monophasic increases a…

Possible mechanisms of action of the antispasmodic agent tiropramide in the isolated detrusor from rats.

The effects of tiropramide hydrochloride on Ca(2+)-induced contraction, cytoplasmic free Ca2+ levels and tissue cyclic AMP concentrations were investigated to elucidate the mechanisms of its antispasmodic action in the isolated detrusor from rats. Tiropramide inhibited the Ca2+ (3 mM)-induced contractions of the isolated urinary bladder depolarized in a Ca(2+)-free medium, and the IC50 value was 3.3 x 10(-6) M. When tiropramide was added during the sustained phase of the K+ (60 mM)-contracture, IC50 values of tiropramide for the contraction and the increased fluorescence were 1.9 x 10(-5) M an

Effects of Cu(II) (3,5-diisopropylsalicylate)2 on soluble protein kinase C activity in rat liver.

The superoxide dismutase mimetic compound, Cu(II) (3,5-diisopropylsalicylate)2 (CuDIPS) inhibited soluble Ca2+/phospholipid dependent protein, kinase (protein kinase C) in rat liver, competing with ATP. The Ca2+/phospholipid- and TPA-stimulated phosphorylation of endogenous proteins were also inhibited by CuDIPS. In vitro and in vivo CuDIPS as well as CuSO4 reduced the activity of TPA-stimulated protein kinase C, while 3,5-diisopropylsalicylate lacked this effect. Our results indicate that CuDIPS interacts with the catalytic domain of the enzyme and the inhibition of protein kinase C may be du

The heterogeneity of rat androgen-binding protein in serum differs from that in testis and epididymis.

Fractionation of testicular, epididymal, and serum extracts containing rat androgen-binding protein (rABP) on a Concanavalin A-Sepharose (Co … rogeneity, we observed that the distribution of the two forms of rABP was the same in the blood and cytosols prepared from testis and epididymis of young rats before the formation of the blood-testis barrier; that is, the ratio of form I to form II ranged from 1:1 to 1:2. Similar heterogeneity was observed in extracts of the reproductive tract from mature …