Search results for "NADP"
showing 10 items of 242 documents
Pharmacological prevention of eNOS uncoupling.
2013
Under physiological conditions, nitric oxide (NO) is produced in the vasculature mainly by the endothelial NO synthase (eNOS). This endothelium-derived NO is a protective molecule with antihypertensive, antithrombotic and anti-atherosclerotic properties. Cardiovascular risk factors such as hypertension, hypercholesterolemia, cigarette smoking and diabetes mellitus induce oxidative stress mostly by stimulation of the NADPH oxidase. Overproduction of reactive oxygen species leads to oxidation of tetrahydrobiopterin (BH4), the essential cofactor of eNOS. In BH4 deficiency, oxygen reduction uncouples from NO synthesis, thereby converting eNOS to a superoxide- producing enzyme. Consequently, NO …
Screening of Ovarian steroidogenic pathway in Ciona intestinalis and its modulation after Tributyltin exposure
2010
In this study, we have identified several ovarian steroids in Ciona with high similarity to vertebrate steroids and showed that cholesterol, corticosterone, dehydroepiandrosterone, estrone, estradiol-17beta, testosterone, pregnenolone, progesterone, have identical molecular spectra with vertebrate steroids. In addition, we have studied the effects of an endocrine disruptor (tributyltin: TBT) on these sex hormones and their precursors, ovarian morphology, and gene expression of some key enzymes in steroidogenic pathway in the ovary of Ciona. Ovarian specimens were cultured in vitro using different concentrations of TBT (10{sup -5}, 10{sup -4} and 10{sup -3} M). Ethanol was used as solvent co…
Downregulation of myogenic microRNAs in sub-chronic but not in sub-acute model of daunorubicin-induced cardiomyopathy
2016
Cardiac muscle-related microRNAs play important roles in cardiac development and disease by translational silencing of mRNAs, the dominant mechanism of microRNA action. To test whether they could be involved in daunorubicin-associated cardiomyopathy (DACM), we determined expression patterns of myomiRs in two distinct models of DACM. We used 10â12 weeks old male Wistar rats. In the sub-acute model, rats were administered with six doses of daunorubicin (DAU-A, 3Â mg/kg, i.p., every 48Â h). Rats were sacrificed two days after the last dose. In the sub-chronic model, anaesthetized rats were administered a single dose of daunorubicin (15Â mg/kg, i.v., DAU-C). Age-matched controls (CON) receive…
Environmental Noise and the Cardiovascular System
2018
Abstract Noise has been found associated with annoyance, stress, sleep disturbance, and impaired cognitive performance. Furthermore, epidemiological studies have found that environmental noise is associated with an increased incidence of arterial hypertension, myocardial infarction, heart failure, and stroke. Observational and translational studies indicate that especially nighttime noise increases levels of stress hormones and vascular oxidative stress, which may lead to endothelial dysfunction and arterial hypertension. Novel experimental studies found aircraft noise to be associated with oxidative stress–induced vascular damage, mediated by activation of the NADPH oxidase, uncoupling of …
Semisynthesis of antitumoral acetogenins: SAR of functionalized alkyl-chain bis-tetrahydrofuranic acetogenins, specific inhibitors of mitochondrial c…
2000
The acetogenins of Annonaceae are known by their potent cytotoxic activity. In fact, they are promising candidates as a new future generation of antitumoral drugs to fight against the current chemiotherapic resistant tumors. The main target enzyme of these compounds is complex I (NADH:ubiquinone oxidoreductase) of the mitochondrial respiratory chain, a key enzymatic complex of energy metabolism. In an attempt to characterize the relevant structural factor of the acetogenins that determines the inhibitory potency against this enzyme, we have prepared a series of bis-tetrahydrofuranic acetogenins with different functional groups along the alkyl chain. They comprise several oxo, hydroxylimino,…
Epoxy-Acetogenins and other Polyketide Epoxy Derivatives as Inhibitors of the Mitochondrial Respiratory Chain Complex I
2000
Annonaceous acetogenins (ACG), an extensive group of cytotoxic natural products, are antitumor agents whose main mode of action is inhibition of the mammalian mitochondrial complex I. Herein we describe the importance of the different chemical groups along the alkyl chain for optimal inhibitory potency, discussing the structurally relevant factors present in these compounds. For this purpose, a series of epoxide derivatives from alpha-linolenic acid were prepared and their activity compared with that of epoxy-acetogenins and tetrahydrofuranic (THF) acetogenins isolated from Rollinia membranacea.
Membrane D-lactate oxidase in Zymomonas mobilis: evidence for a branched respiratory chain.
1998
Respiratory chain composition of the ethanol-producing bacterium Zymomonas mobilis was studied. Its membrane D-lactate oxidase was characterised. With NADH, but not D-lactate as substrate, a cytochrome o-like component was seen in CO difference spectra. Chlorpromazine specifically inhibited reduction of cytochrome d, while myxothiazol eliminated the cytochrome o-like features in CO difference spectra. It is suggested that electrons from NADH are distributed between branches terminated by the cytochrome o-like component, cytochrome a, and cytochrome d. With D-lactate, electrons are transported to cytochrome a, or an unidentified CN(-)-sensitive oxidase, and cytochrome d.
Gamma-lactone-Functionalized antitumoral acetogenins are the most potent inhibitors of mitochondrial complex I.
2001
To study the relevance of the terminal alpha,beta-unsaturated gamma-methyl-gamma-lactone moiety of the antitumoral acetogenins of Annonaceae for potent mitochondrial complex I inhibition, we have prepared a series of semisynthetic acetogenins with modifications only in this part of the molecule, from the natural rolliniastatin-1 (1) and cherimolin-1 (2). Some of the hydroxylated derivatives (1b, 1d and 1e) in addition to two infrequent natural beta-hydroxy gamma-methyl gamma-lactone acetogenins, laherradurin (3) and itrabin (4), are more potent complex I inhibitors than any other known compounds.
Natural substances (acetogenins) from the family Annonaceae are powerful inhibitors of mitochondrial NADH dehydrogenase (Complex I).
1994
Natural products from the plants of the family Annonaceae, collectively called Annonaceous acetogenins, are very potent inhibitors of the NADH-ubiquinone reductase (Complex I) activity of mammalian mitochondria. The properties of five of such acetogenins are compared with those of rotenone and piericidin, classical potent inhibitors of Complex I. Rolliniastatin-1 and rolliniastatin-2 are more powerful than piericidin in terms of both their inhibitory constant and the protein-dependence of their titre in bovine submitochondrial particles. These acetogenins could be considered therefore the most potent inhibitors of mammalian Complex I. Squamocin and otivarin also have an inhibitory constant …
Bisbenzyltetrahydroisoquinolines, a New Class of Inhibitors of the Mitochondrial Respiratory Chain Complex I
2004
Four bisbenzyltetrahydroisoquinoline alkaloids (-)-medelline, (+)-antioquine, (+)-aromoline, and (+)-obamegine were isolated from the fruits of Xylopia columbiana. These compounds, the previously isolated alkaloids (+)-thaligrisine and (+)-isotetrandrine, as well as their O-acetylated derivatives were assayed on submitochondrial particles from beef heart as inhibitors of the mammalian respiratory chain. The results revealed that these alkaloids act as selective inhibitors of mitochondrial complex I in a 0.15 - 4.71 microM range. O-Acetylation, which increases their lipophilicity, considerably increased the inhibitory potency.