Hepoxilin A(3) protects β-cells from apoptosis in contrast to its precursor, 12-hydroperoxyeicosatetraenoic acid.

Pancreatic β-cells have a deficit of scavenging enzymes such as catalase (Cat) and glutathione peroxidase (GPx) and therefore are susceptible to oxidative stress and apoptosis. Our previous work showed that, in the absence of cytosolic GPx in insulinoma RINm5F cells, an intrinsic activity of 12 lipoxygenase (12(S)-LOX) converts 12S-hydroperoxyeicosatetraenoic acid (12(S)-HpETE) to the bioactive epoxide hepoxilin A(3) (HXA(3)). The aim of the present study was to investigate the effect of HXA(3) on apoptosis as compared to its precursor 12(S)-HpETE and shed light upon the underlying pathways.

C. albicans activates cyclooxygenase but not its product prostaglandin E₂in HPV 16-stabilized cells.

Objective: The selective induction of cyclooxygenase-2 (COX-2) in human cells by Candida albicans was the first report of its role in infectious disease. This led us to question whether recurrent vulvovaginal candidosis in the cancer patient is involved in the formation of malignant tumors of the genital tract. Our speculation coincided with the patients' assessments in our hospital, where few cancer patients had a prior history of Candida infection.

On mechanism of quorum sensing in Candida albicans by 3(R)-hydroxy-tetradecaenoic acid.

Quorum sensing (QS) enables microorganisms to monitor their own density of population, and also their pathogenicity by intracellular signals, and synchronizing their specialized gene system in a particular cell density. QS system has been shown in Candida sp. as switching mechanism between successive phases in Candida cell morphology.

Sperm motility in the fishes of pesticide exposed and from polluted rivers of Gomti and Ganga of north India.

Investigation of lethal dose of gamma-HCH (gamma isomer of hexachlorocyclohexane), DDT (dichlorodiphenyltrichloroethane) and chlorpyrifos on spermatozoa motility after 40 days exposure in catfish, Heteropneustes fossilis was done under laboratory conditions. The sperm motility was done in the fishes captured from unpolluted ponds of Gujartal considering as reference site and polluted rivers Gomti and Ganga of north India at pre-spermiating stage. Results indicate that 1ppm of gamma-HCH, DDT and chlorpyrifos was lethal dose on sperm motility.

Candida albicans modulates host defense by biosynthesizing the pro-resolving mediator resolvin E1.

Candida albicans is an opportunistic fungal pathogen of humans that resides commensally on epithelial surfaces, but can cause inflammation when pathogenic. Resolvins are a class of anti-inflammatory lipids derived from omega-3 polyunsaturated fatty acids (PUFA) that attenuate neutrophil migration during the resolution phase of inflammation. In this report we demonstrate that C.

Hepoxilin A3 (HXA3) synthase deficiency is causative of a novel ichthyosis form.

Non-bullous congenital ichthyosis erythroderma (NCIE) and lamellar ichthyosis (LI) are characterized by mutations in 12R-lipoxygenase (12R-LOX) and/or epidermal lipoxygenase 3 (eLOX3) enzymes. The eLOX3 lacks oxygenase activity, but is capable of forming hepoxilin-type products from arachidonic acid-derived hydroperoxide from 12R-LOX, termed 12R-hydroperoxyeicosa-5,8,10,14-tetraenoic acid (12R-HpETE). Mutations in either of two enzymes lead to NCIE or LI.

Increased endocannabinoid levels reduce the development of precancerous lesions in the mouse colon.

Colorectal cancer is an increasingly important cause of death in Western countries. Endocannabinoids inhibit colorectal carcinoma cell proliferation in vitro. In this paper, we investigated the involvement of endocannabinoids on the formation of aberrant crypt foci (ACF, earliest preneoplastic lesions) in the colon mouse in vivo.

Structure, biochemistry and biology of hepoxilins: an update.

Hepoxilins are biologically relevant epoxy-hydroxy eicosanoids synthesized through the 12S-lipoxygenase (12S-LOX) pathway of the arachidonic acid (AA) metabolism. The pathway is bifurcated at the level of 12S-hydroperoxy-eicosatetraenoic acid (12S-HpETE), which can either be reduced to 12S-hydro-eicosatetraenoic acid (12S-HETE) or converted to hepoxilins. The present review gives an update on the biochemistry, biology and clinical aspects of hepoxilin-based drug development.

Mechanisms for the coupling of cannabinoid receptors to intracellular calcium mobilization in rat insulinoma beta-cells.

In RIN m5F rat insulinoma beta-cells, agonists at cannabinoid CB(1) receptors modulate insulin release. Here we investigated in these cells the effect of the activation of cannabinoid CB(1) and CB(2) receptors on intracellular Ca(2+) ([Ca(2+)](i)). The CB(1) agonist arachidonoyl-chloro-ethanolamide (ACEA), and the CB(2) agonist JWH133, elevated [Ca(2+)](i) in a way sensitive to the inhibitor of phosphoinositide-specific phospholipase C (PI-PLC), U73122 (but not to pertussis toxin and forskolin), and independently from extracellular Ca(2+).

The ubiquitin- and proteasome-dependent degradation of COX-2 is regulated by the COP9 signalosome and differentially influenced by coxibs.

The cyclooxygenase-2 (COX-2) enzyme is induced upon inflammation and in neoplastic tissues. It produces prostaglandins that stimulate tumor angiogenesis and tumor growth. Therefore, destruction and/or specific inhibition of COX-2 should be an important aspect of future tumor therapy.

Overactivity of the intestinal endocannabinoid system in celiac disease and in methotrexate-treated rats.

The endocannabinoid system is upregulated in both human inflammatory bowel diseases and experimental models of colitis. In this study, we investigated whether this upregulation is a marker also of celiac disease-induced atrophy. The levels of the cannabinoid CB(1) receptor, of the endocannabinoids, anandamide, and 2-arachidonoyl-glycerol (2-AG), and of the anti-inflammatory mediator palmitoylethanolamide (PEA) were analyzed in bioptic samples from the duodenal mucosa of celiac patients at first diagnosis assessed by the determination of antiendomysial antibodies and histological examination.

Biochemistry and pharmacology of endovanilloids.

Endovanilloids are defined as endogenous ligands and activators of transient receptor potential (TRP) vanilloid type 1 (TRPV1) channels. The first endovanilloid to be identified was anandamide (AEA), previously discovered as an endogenous agonist of cannabinoid receptors. In fact, there are several similarities, in terms of opposing actions on the same intracellular signals, role in the same pathological conditions, and shared ligands and tissue distribution, between TRPV1 and cannabinoid CB(1) receptors.

The release of elongated, sheathed ascospores from bottle-shaped asci in Dipodascus geniculatus.

Yeasts use different mechanisms to release ascospores of different lengths from bottle-shaped asci. Round to oval-shaped ascospores are enveloped in oxylipin-coated compressible sheaths, enabling ascospores to slide past each other when they reach the narrowing ascus neck. However, more elongated ascospores do not contain sheaths, but are linked by means of oxylipin-coated interlocked hooked ridges on the surfaces of neighboring ascospores, thereby keeping them aligned while they are pushed towards the ascus tip by turgor pressure.

Oxylipin-coated hat-shaped ascospores of Ascoidea corymbosa.

We previously implicated 3-hydroxy oxylipins and ascospore structure in ascospore release from enclosed asci. Using confocal laser scanning microscopy on cells stained with fluorescein-coupled, 3-hydroxy oxylipin-specific antibodies, we found that oxylipins are specifically associated with ascospores and not the vegetative cells or ascus wall of Ascoidea corymbosa. Using gas chromatography--mass spectrometry the oxylipin 3-hydroxy 17:0 could be identified.

Phospholipase A2 and phospholipase B activities in fungi.

As saprophytes or disease causing microorganisms, fungi acquire nutrients from dead organic material or living host organisms. Lipids as structural components of cell membranes and storage compartments play an important role as energy-rich food source. In recent years, it also has become clear that lipids have a wide range of bioactive properties including signal transduction and cell to cell communication.

Inactivation of the phospholipase B gene PLB5 in wild-type Candida albicans reduces cell-associated phospholipase A2 activity and attenuates virulence.

Phospholipases are critical for modification and redistribution of lipid substrates, membrane remodeling and microbial virulence. Among the many different classes of phospholipases, fungal phospholipase B (Plb) proteins show the broadest range of substrate specificity and hydrolytic activity, hydrolyzing acyl ester bonds in phospholipids and lysophospholipids and further catalyzing lysophospholipase-transacylase reactions. The genome of the opportunistic fungal pathogen Candida albicans encodes a PLB multigene family with five putative members; we present the first characterization of this group of potential virulence determinants.

Mapping the distribution of 3-hydroxy oxylipins in the ascomycetous yeast Saturnispora saitoi.

The distribution of 3-hydroxy oxylipins in Saturnispora saitoi was mapped using immunofluorescence microscopy. Fluorescence was observed on aggregating ascospores, indicating the presence of 3-hydroxy oxylipins on the surface or between ascospores. The oxylipin was identified as 3-hydroxy 9:1 using gas chromatography mass spectrometry.

Hepoxilin A3 synthase.

Hepoxilins constitute a group of 12S-hydroperoxyeicosatetraenoic acid (12S-HpETE)-derived epoxy-hydroxy fatty acids that have been detected in various cell types and tissues. Although hepoxilin A3 (HXA3) exhibits a myriad of biological activities, its biosynthetic mechanism was not investigated in detail. Here we review the isolation, cloning, and characterization of a leukocyte-type 12S-lipoxygenase (12S-LOX) from rat insulinoma cells RINm5F, which exhibits an intrinsic hepoxilin A3 synthase activity.

The presence of 3-hydroxy oxylipins on the ascospore surfaces of some species representing Saccharomycopsis Schiönning.

Through gas chromatography - mass spectrometry, the presence of oxylipins, mainly 3-hydroxy 9:1 and 3-hydroxy 10:1, was detected in Saccharomycopsis fermentans, Saccharomycopsis javanensis, and Saccharomycopsis vini. The distribution of these compounds was mapped using immunofluorescence microscopy, and they were found to be closely associated with the surfaces of aggregating ascospores.

Ascospore release from bottle-shaped asci in Dipodascus albidus.

Yeasts utilize different mechanisms to release ascospores of different lengths from bottle-shaped asci. Using electron microscopy, confocal laser scanning microscopy, gas chromatography-mass spectrometry and digital live imaging, the individual release of oval ascospores from tight-fitting narrow bottle-necks, is reported in the yeast Dipodascus albidus. These ascospores are surrounded by compressible, oxylipin-coated sheaths enabling ascospores to slide past each other when forced by turgor pressure and by possible sheath contractions towards the narrowing ascus-neck.

Oxygenation by COX-2 (cyclo-oxygenase-2) of 3-HETE (3-hydroxyeicosatetraenoic acid), a fungal mimetic of arachidonic acid, produces a cascade of novel bioactive 3-hydroxyeicosanoids.

Cyclo-oxygenases-1/2 (COX-1/2) catalyse the oxygenation of AA (arachidonic acid) and related polyunsaturated fatty acids to endoperoxide precursors of prostanoids. COX-1 is referred to as a constitutive enzyme involved in haemostasis, whereas COX-2 is an inducible enzyme expressed in inflammatory diseases and cancer. The fungus Dipodascopsis uninucleata has been shown by us to convert exogenous AA into 3(R)-HETE [3(R)-hydroxy-5Z,8Z,11Z,14Z-eicosatetraenoic acid].

The presence of novel 3-hydroxy oxylipins on surfaces of hat-shaped ascospores of Ascoidea africana Batra & Francke-Grosmann.

Immunofluorescence microscopy exposed the presence of novel 3-hydroxy oxylipins on the surfaces of aggregated hat-shaped ascospores of Ascoidea africana. These compounds were confirmed by gas chromatography - mass spectrometry analysis. Only the complete structure of a novel 3-hydroxy 10:1 could be determined.

Report on the discovery of a novel 3-hydroxy oxylipin cascade in the yeast Saccharomycopsis synnaedendra.

A novel cascade of 3-hydroxy fatty acids was discovered in the yeast Saccharomycopsis synnaedendra. The cascade, probably derived from incomplete beta-oxidation, comprises both even and uneven carbon numbered as well as saturated and unsaturated 3-hydroxy oxylipins. This yeast may now be used as model to further study the metabolism of these compounds as well as their biotechnological production.

The rat leukocyte-type 12-lipoxygenase exhibits an intrinsic hepoxilin A3 synthase activity.

Hepoxilins are biologically relevant eicosanoids formed via the 12-lipoxygenase pathway of the arachidonic acid cascade. Although these eicosanoids exhibit a myriad of biological activities, their biosynthetic mechanism has not been investigated in detail. We examined the arachidonic acid metabolism of RINm5F rat insulinoma cells and found that they constitutively express a leukocyte-type 12S-lipoxygenase.