Organic cation/carnitine transporter OCTN3 is present in astrocytes and is up-regulated by peroxisome proliferators-activator receptor agonist

In the brain β-oxidation, which takes place in astrocytes, is not a major process of energy supply. Astrocytes synthesize important lipid metabolites, mainly due to the processes taking place in peroxisomes. One of the compounds necessary in the process of mitochondrial β-oxidation and export of acyl moieties from peroxisomes is l-carnitine. Two Na-dependent plasma membrane carnitine transporters were shown previously to be present in astrocytes: a low affinity amino acid transporter B^0,+ and a high affinity cation/carnitine transporter OCTN2. The expression of OCTN2 is known to increase in peripheral tissues upon the stimulation of peroxisome proliferators-activator receptor α (PPARα), a nuclear receptor known to up-regulate several enzymes involved in fatty acid metabolism. The present study was focused on another high affinity carnitine transporter—OCTN3, its presence, regulation and activity in astrocytes. Experiments using the techniques of real-time PCR, Western blot and immunocytochemistry analysis demonstrated the expression of octn3 in rat astrocytes and, out of two rat sequences ascribed as similar to mouse OCTN3, XM_001073573 was found in these cells. PPARα activator–2-[4-chloro-6-[(2,3-dimethylphenyl)amino]-2-pyrimidinyl]thio]acetic acid (WY-14,643) stimulated by 50% expression of octn3, while, on the contrary to peripheral tissues, it did not change the expression of octn2. This observation was correlated with an increased Na-independent activity of carnitine transport. Analysis by transmission electron microscopy showed an augmented intracellular localization of OCTN3 upon PPARα stimulation, mainly in peroxisomes, indicating a physiological role of OCTN3 as peroxisomal membrane transporter. These observations point to an important role of OCTN3 in peroxisomal fatty acid metabolism in astrocytes.     

Perturbation of the lipid phase of a membrane is not involved in the modulation of MRP1 transport activity by flavonoids

The expression of transmembrane transporter multidrug resistance-associated protein 1 (MRP1) confers the multidrug-resistant phenotype (MDR) on cancer cells. Since the activity of the other MDR transporter, P-glycoprotein, is sensitive to membrane perturbation, we aimed to check whether the changes in lipid bilayer properties induced by flavones (apigenin, acacetin) and flavonols (morin, myricetin) were related to their MRP1 inhibitory activity. All the flavonoids inhibited the efflux of MRP1 fluorescent substrate from human erythrocytes and breast cancer cells. Morin was also found to stimulate the ATPase activity of erythrocyte ghosts. All flavonoids intercalated into phosphatidylcholine bilayers as judged by differential scanning calorimetry and fluorescence spectroscopy with the use of two carbocyanine dyes. The model of an intramembrane localization for flavones and flavonols was proposed. No clear relationship was found between the membrane-perturbing activity of flavonoids and their potency to inhibit MRP1. We concluded that mechanisms other than perturbation of the lipid phase of membranes were responsible for inhibition of MRP1 by the flavonoids.     

Search for alpha-glucosidase inhibitors: new N-substituted valienamine and conduramine F-1 derivatives

A solid-phase synthesis of new N-substituted valienamines has been developed and new synthesis of (+/-)-conduramine F-1, (-)-conduramine F-1, and (+)-ent-conduramine F-1 is presented, together with the preparation of N-benzylated conduramines F-1. N-Benzylation of both valienamine and (+)-ent-conduramine F-1 improves their inhibitory activity toward alpha-glucosidases significantly. The additional hydroxymethyl group makes valienamine derivatives more active than their (+)-ent-conduramine F-1 analogues.     

The effects of percutaneous transluminal coronary intervention on biomarkers of oxidative stress in the erythrocytes of elderly male patients

Objectives: Oxidative stress plays a key role in the pathogenesis of coronary artery disease. The aim of this study was to compare the effects of percutaneous transluminal coronary angioplasty (PTCA) and elective coronary angiography (EC) on erythrocytic antioxidant defense in elderly male patients.

Methods: Twenty-three stable angina pectoris (SAP) patients undergoing PTCA and 18 patients with ischemic symptoms scheduled to undergo diagnostic EC were included in the study. The concentrations of malondialdehyde (MDA) and reduced glutathione (GSH) and the activities of Zn,Cu-superoxide dismutase (SOD-1), catalase (CAT), and cytosolic glutathione peroxidase (GSH-Px) were examined in the erythrocytes before, immediately after and 2 weeks following PTCA or EC.

Results: The MDA concentrations were significantly higher and SOD-1, CAT, and GSH-Px activities were significantly lower in the PTCA group than in the EC group at baseline. Two weeks after treatment, the activities of the enzymes significantly increased in both groups, whereas the MDA concentrations decreased only in the PTCA patients.

Conclusions: The results confirm that an advanced state of atherosclerosis is related to greater levels of oxidative stress. The study indicates that both procedures may induce antioxidant defenses; however, PTCA exclusively induces a long-term reduction in lipid peroxidation.     

The effect of experimental exposure to low doses of zearalenone on uterine histology and morphometry in prepubertal bitches

The experiment involved 30 clinically healthy prepubertal bitches aged approximately 70 days with an estimated initial body weight (BW) of 8 kg. The animals were randomly divided into two experimental groups (EI and EII) and a control group of 10 animals each. Group EI was administered 50 μg zearalenone (ZEN)/kg BW per os for 42 days, group EII received 75 μg zearalenone/kg BW per os for 42 days, and the control group was administered placebo per os for 42 days. The bitches were hysterectomized at the end of treatment, and samples of uterine tissue were collected for histological and morphometric analyses. The results of the study indicate that exposure to very low doses of ZEN (100% and 150% of the NOAEL) causes simple glandular hyperplasia of the endometrium accompanied by adenogenesis, angiogenesis, and vasodilatation with the related consequences. The noted changes were more pronounced in group EI and less visible in group EII in comparison with group C, which could be indicative of a hormetic dose response.     

Proterozoic phytoplankton and timing of Chlorophyte algae origins

Abstract: Morphological and reproductive features and cell wall ultrastructure and biochemistry of Proterozoic acritarchs are used to determine their affinity to modern algae. The first appearance datum of these microbiota is traced to infer a minimum age of the divergence of the algal classes to which they may belong. The chronological appearance of microfossils that represent phycoma‐like and zygotic cysts and vegetative cells and/or aplanospores, respectively, interpreted as prasinophyceaen and chlorophyceaen microalgae is related to the Viridiplantae phylogeny. An inferred minimum age of the Chlorophyte origin is before c. 1800 Ma, the Prasinophyceae at c. 1650 Ma and the Chlorophyceae at c. 1450 Ma. These divergence times differ from molecular clock estimates, and the palaeontological evidence suggests that they are older.     

Microconchid tubeworms across the upper Frasnian – lower Famennian interval in the Central Devonian Field,Russia

Abstract: Microconchid tubeworms (Tentaculita) encrusting brachiopod shells have been investigated from the upper Frasnian – lower Famennian (Upper Devonian) deposits of the Central Devonian Field, Russia. The condition of microconchids and associated encrusting taxa is reported for the first time from the early Famennian recovery interval (crepida Chron) following the Frasnian–Famennian mass extinction. Two species, one new (Palaeoconchus variabilis sp. nov.) and the second one in open nomenclature (Palaeoconchus sp.), are described. Compared to lower Famennian specimens, they seem to be preferentially grouped on the anterior parts of the brachiopod host shells, which are interpreted as the most suitable sites away from the sea‐bottom and sediment. During the late Frasnian (Late rhenana Chron), microconchids, outnumbered by cornulitids and as abundant as foraminifers, were also associated with trepostome bryozoans, tabulates, rugose corals and various problematic encrusters. During the early Famennian recovery interval encompassing the crepida Chron, microconchids greatly outnumbered all associated encrusters, including the previously dominant cornulitids, while foraminifers, tabulates and rugose corals vanished. Early Famennian microconchids, represented by the single, albeit very abundant, species Palaeoconchus variabilis sp. nov., were opportunists that rapidly colonised the environment during the ongoing transgression following the regression‐driven biotic crisis in the area of the Central Devonian Field. In comparison to their late Frasnian predecessors and even other Middle Devonian specimens, no size reduction (the so‐called Lilliput effect) of early Famennian microconchid tubes was observed. It is probable that microconchids either rapidly attained their ‘normal’ sizes or they did not suffer any dwarfism following the Frasnian–Famennian event.     

The significance of peroxisomes in secondary metabolite biosynthesis in filamentous fungi

Peroxisomes are ubiquitous organelles characterized by a protein-rich matrix surrounded by a single membrane. In filamentous fungi, peroxisomes are crucial for the primary metabolism of several unusual carbon sources used for growth (e.g. fatty acids), but increasing evidence is presented that emphasize the crucial role of these organelles in the formation of a variety of secondary metabolites. In filamentous fungi, peroxisomes also play a role in development and differentiation whereas specialized peroxisomes, the Woronin bodies, play a structural role in plugging septal pores. The biogenesis of peroxisomes in filamentous fungi involves the function of conserved PEX genes, as well as genes that are unique for these organisms. Peroxisomes are also subject to autophagic degradation, a process that involves ATG genes. The interplay between organelle biogenesis and degradation may serve a quality control function, thereby allowing a continuous rejuvenation of the organelle population in the cells.     

Membrane curvature during peroxisome fission requires Pex11

Pex11 is a key player in peroxisome proliferation, but the molecular mechanisms of its function are still unknown. Here, we show that Pex11 contains a conserved sequence at the N-terminus that can adopt the structure of an amphipathic helix. Using Penicillium chrysogenum Pex11, we show that this amphipathic helix, termed Pex11-Amph, associates with liposomes in vitro. This interaction is especially evident when negatively charged liposomes are used with a phospholipid content resembling that of peroxisomal membranes. Binding of Pex11-Amph to negatively charged membrane vesicles resulted in strong tubulation. This tubulation of vesicles was also observed when the entire soluble N-terminal domain of Pex11 was used. Using mutant peptides, we demonstrate that maintaining the amphipathic properties of Pex11-Amph in conjunction with retaining its α-helical structure are crucial for its function. We show that the membrane remodelling capacity of the amphipathic helix in Pex11 is conserved from yeast to man. Finally, we demonstrate that mutations abolishing the membrane remodelling activity of the Pex11-Amph domain also hamper the function of full-length Pex11 in peroxisome fission in vivo.     

Plant and animal cuticle remains from the Lower Devonian of southern Poland and their palaeoenvironmental significance

Filipiak, P. & Zatoń, M. 2010: Plant and animal cuticle remains from the Lower Devonian of southern Poland and their palaeoenvironmental significance. Lethaia, Vol. 44, pp. 397–409. Assemblages of plant and arthropod remains are reported from the Lower Devonian clastic deposits of the Upper Silesian and Ma?opolska blocks in southern Poland. Most of the plant and animal remains are palynologically dated as Pragian–Emsian/Eifelian. The plant material comprises higher plant cuticles with stomata classified as Drephanophycus and Sawdonia, and more enigmatic remains (nematophytes) classified as Nematothallus, Cosmochlaina and tubular banded tubes. They are associated with abundant and diverse miospores. Animal remains consist of eurypterid respiratory organs, the morphology of which may presumably point to their advance physiological properties, and cuticular remains of eurypterid and probably scorpion origin, as well as some remains of unknown affinity. The presence of such mixed assemblages in the Lower Devonian of Poland indicate marginal‐marine and/or alluvial environments spreading in the southern margin of the Old Red Continent. The dominance of land‐derived plant remains and simultaneous scarcity of marine acritarchs indicate that the environment was very weakly influenced by marine conditions. If nematophytes were really related to extant liverworts, as suggested by some workers, they, together with the other associated spore‐producing plants, may strongly indicate moist environmental conditions, which may have offered suitable habitats for temporary eurypterid migrations onto land. □Cuticles, eurypterids, Lower Devonian, nematophytes, Poland, spores.