Search results for "REDUCTASE"

Heme oxygenase-1 induction modulates microsomal prostaglandin E synthase-1 expression and prostaglandin E2 production in osteoarthritic chondrocytes

2009

Pro-inflammatory cytokines such as interleukin-1beta (IL-1beta) may participate in the pathogenesis of cartilage damage in osteoarthritis (OA) through the production of catabolic enzymes and inflammatory mediators. Induction of heme oxygenase-1 (HO-1) has previously been shown to exert anti-inflammatory effects in different cell types. We have investigated whether HO-1 induction may modify chondrocyte viability and the production of relevant mediators such as oxidative stress and prostaglandin E(2) (PGE(2)) elicited by IL-1beta in OA chondrocytes. Chondrocytes were isolated from OA cartilage and used in primary culture. Cells were stimulated with IL-1beta in the absence or presence of the H…

Ionizing radiation-induced E-selectin gene expression and tumor cell adhesion is inhibited by lovastatin and all-trans retinoic acid

2004

E-selectin mediated tumor cell adhesion plays an important role in metastasis. Here we show that ionizing radiation (IR) induces E-selectin gene and protein expression in human endothelial cells at therapeutically relevant dose level. E-selectin expression is accompanied by an increase in the adhesion of human colon carcinoma cells to primary human umbilical vein endothelial cells (HUVEC). The HMG-CoA reductase inhibitor lovastatin impairs IR-stimulated E-selectin expression as analyzed at the level of the protein, mRNA and promoter. Inactivation of Rho GTPases either by use of Clostridium difficile toxin A or by co-expression of dominant-negative Rho blocked IR-induced E-selectin gene indu…

Oxidative stress induces distinct physiological responses in the two Trebouxia phycobionts of the lichen Ramalina farinacea

2010

† Background and Aims Most lichens form associations with Trebouxia phycobionts and some of them simultaneously include genetically different algal lineages. In other symbiotic systems involving algae (e.g. reef corals), the relative abundances of different endosymbiotic algal clades may change over time. This process seems to provide a mechanism allowing the organism to respond to environmental stress. A similar mechanism may operate in lichens with more than one algal lineage, likewise protecting them against environmental stresses. Here, the physiological responses to oxidative stress of two distinct Trebouxia phycobionts (provisionally named TR1 and TR9) that coexist within the lichen R…

Different strategies to achieve Pb-tolerance by the two Trebouxia algae coexisting in the lichen Ramalina farinacea.

2012

Lichen thalli are permeable to airborne substances, including heavy metals, which are harmful to cell metabolism. Ramalina farinacea shows a moderate tolerance to Pb. This lichen comprises two Trebouxia phycobionts, provisionally referred to as TR1 and TR9, with distinct physiological responses to acute oxidative stress. Thus, there is a more severe decay in photosynthesis and photosynthetic pigments in TR1 than in TR9. Similarly, under oxidative stress, antioxidant enzymes and HSP70 protein decrease in TR1 but increase in TR9. Since Pb toxicity is associated with increased ROS formation, we hypothesized greater Pb tolerance in this phycobiont. Accordingly, the aim of the present study was …

Predicting 19F NMR Chemical Shifts: A Combined Computational and Experimental Study of a Trypanosomal Oxidoreductase–Inhibitor Complex

2020

Abstract The absence of fluorine from most biomolecules renders it an excellent probe for NMR spectroscopy to monitor inhibitor–protein interactions. However, predicting the binding mode of a fluorinated ligand from a chemical shift (or vice versa) has been challenging due to the high electron density of the fluorine atom. Nonetheless, reliable 19F chemical‐shift predictions to deduce ligand‐binding modes hold great potential for in silico drug design. Herein, we present a systematic QM/MM study to predict the 19F NMR chemical shifts of a covalently bound fluorinated inhibitor to the essential oxidoreductase tryparedoxin (Tpx) from African trypanosomes, the causative agent of African sleepi…

Inhibitor-Induced Dimerization of an Essential Oxidoreductase from African Trypanosomes

2018

Trypanosomal and leishmanial infections claim tens of thousands of lives each year. The metabolism of these unicellular eukaryotic parasites differs from the human host and their enzymes thus constitute promising drug targets. Tryparedoxin (Tpx) from Trypanosoma brucei is the essential oxidoreductase in the parasite's hydroperoxide-clearance cascade. In vitro and in vivo functional assays show that a small, selective inhibitor efficiently inhibits Tpx. With X-ray crystallography, SAXS, analytical SEC, SEC-MALS, MD simulations, ITC, and NMR spectroscopy, we show how covalent binding of this monofunctional inhibitor leads to Tpx dimerization. Intra- and intermolecular inhibitor-inhibitor, pro…

Vomilenine Reductase — a novel Enzyme catalyzing a crucial Step in the Biosynthesis of the Therapeutically applied Antiarrhythmic Alkaloid Ajmaline

2002

Delineation of the biochemical pathway leading to the antiarrhythmic Rauvolfia alkaloid ajmaline has been an important target in biosynthetic research for many years. The biosynthetic sequence starting with tryptamine and the monoterpene secologanin consists of about 10 different steps. Most of the participating enzymes have been detected and characterized previously, except those catalyzing the reduction of the intermediate vomilenine. A novel NADPH-dependent enzyme that reduces the intermediate has been isolated from Rauvolfia serpentina cell suspension cultures. Vomilenine reductase (M(r )43 kDa, temp opt 30 degrees C, pH opt 5.7-6.2), saturates the indolenine double bond of vomilenine w…

Asymptomatic Carotid Lesion as a Marker of Future Cerebrovascular and Cardiovascular Events

2003

Novel inhibitors of mitochondrial respiratory chain: endoperoxides from the marine tunicate Stolonica socialis.

2001

The Mediterranean tunicate Stolonica socialis contains a new class of powerful cytotoxic acetogenins, generically named stolonoxides. In this paper, which also details the isolation and chemical characterization of a minor component (3a) of the tunicate extract, we report the potent inhibitory activity (IC(50) < 1 microM) of stolonoxides (1a and 3a) on mitochondrial electron transfer. The compounds affect specifically the functionality of complex II (succinate:ubiquinone oxidoreductase) and complex III (ubiquinol:cytochrome C oxidoreductase) in mammalian cells, thereby causing a rapid collapse of the whole energetic metabolism. This result, which differs from the properties of similar known…

Kinetic characterization of mitochondrial complex I inhibitors using annonaceous acetogenins

1999

The NADH:ubiquinone oxidoreductase (complex I) of the mitochondrial respiratory chain is by far the largest and most complicated of the proton-translocating enzymes involved in the oxidative phosphorylation. Many clues regarding the electron pathways from matrix NADH to membrane ubiquinone and the links of this process with the translocation of protons are highly controversial. Different types of inhibitors become valuable tools to dissect the electron and proton pathways of this complex enzyme. Therefore, further knowledge of the mode of action of complex I inhibitors is needed to understand the underlying mechanism of energy conservation. This study presents for the first time a detailed …