Inhibition of pannexin-1 channel activity by adiponectin in podocytes: Role of acid ceramidase activation

The pannexin-1 (Panx1) channel has been reported to mediate the release of ATP that is involved in local tissue inflammation, obesity, and many chronic degenerative diseases. It remains unknown whether Panx1 is present in podocytes and whether this channel in podocytes mediates ATP release leading to glomerular inflammation or fibrosis. To answer these questions, we first characterized the expression of Panx channels in podocytes. Among the three known pannexins, Panx1 was the most enriched in podocytes, either cultured or native in mouse glomeruli. Using a Port-a-Patch planar patch-clamp system, we recorded a large voltage-gated outward current through podocyte membrane under the Cs⁺in/Na⁺out gradient. Substitution of gluconate or aspartate for chloride in the bath solution blocked voltage-gated outward currents and shifted the reversal potential of Panx1 currents to the right, indicating the anion permeability of this channel. Pharmacologically, the recorded voltage-gated outward currents were substantially attenuated by specific Panx1 channel inhibitors. Given the anti-inflammatory and intracellular ATP restorative effects of adiponectin, we tested whether this adipokine inhibits Panx1 channel activity to block ATP release. Adiponectin blocked Panx1 channel activity in podocytes. Mechanistically, inhibition of acid ceramidase (AC) remarkably enhanced Panx1 channel activity under control conditions and prevented the inhibition of Panx1 channel by adiponectin. Correspondingly, intracellular addition of AC products, sphingosine or sphingosine-1-phosphate (S1P), blocked Panx1 channel activity, while elevation of intracellular ceramide had no effect on Panx1 channel activity. These results suggest that adiponectin inhibits Panx1 channel activity in podocytes through activation of AC and associated elevation of intracellular S1P.     

Attenuated satiation response to intestinal nutrients in rats that do not express CCK-A receptors.

Pharmacological experiments suggest that satiation associated with intestinal infusion of several nutrients is mediated by CCK-A receptors. Otsuka Long-Evans Tokushima Fatty, (OLETF), rats do not express CCK-A receptors and are insensitive to the satiation-producing effects of exogenous CCK. To further evaluate the role of CCK-A receptors in satiation by intestinal nutrient infusion, we examined intake of solid (pelleted rat chow) or liquid (12.5% glucose) food intake, following intestinal infusions of fats (oleic acid or fat emulsion), sugars (maltotriose or glucose), or peptone in OLETF rats and Long Evans Tokushima Otsuka control rats (LETO). Intestinal infusion of glucose or maltotriose reduced solid food intake more in LETO than in OLETF rats from 30 min through 4 h post infusion. Reduction of solid food intake by intestinal infusions of fat or peptone did not differ between OLETF and LETO rats during the first 30 min post infusion, but reduction of intake by these infusates was attenuated in OLETF rats over the ensuing 4h post infusion. Intestinal infusion of glucose, oleate, fat emulsion and peptone reduced 30-min intake of 12.5% glucose more in LETO than OLETF rats. Furthermore, pretreatment with the CCK-A receptor antagonist, devazepide, attenuated intestinal nutrient-induced reduction of food intake only in LETO, but not OLETF rats. Our results confirm pharmacological results, indicating that CCK-A receptors participate in satiation by nutrients that elevate plasma CCK concentrations, as well as by nutrients that do not stimulate secretion of endocrine CCK. In addition, our results indicate: 1) that OLETF rats have deficits in the satiation response to a variety of intestinal nutrient infusions; 2) that the temporal pattern for CCK-A receptor participation in satiation by intestinal nutrients is different during ingestion of liquid and solid foods and 3) that intestinal nutrients provide some satiation signals that are CCK-A receptor mediated and some that are not.     

Envirovet Summer Institute: Integrating Veterinary Medicine into Ecosystem Health Practice

Since 1991, Envirovet Summer Institutes have provided an intensive educational program in wildlife and ecosystem health to approximately 225 animal health professionals. Envirovet provides knowledge, skills, and multiple mentors to catalyze ecosystem health-oriented careers for young veterinarians. It is a total immersion experience, with the students engaged in 60–70 hours a week of instruction, 6–7 days a week, for 6 weeks. The course is comprised of lecture, laboratory, and field experiences organized into three sessions: 1) terrestrial wildlife and ecosystem health; 2) aquatic wildlife and ecosystem health; and 3) an ecosystem health approach to international development. Sessions 1 and 2 take place in Florida and Georgia; Session 3 takes place in a developing country (e.g., Kenya, Brazil, South Africa). Ultimately, the goal of Envirovet is to increase the numbers and effectiveness of veterinarians in productive ecosystem health research and application teams around the world.     

Studies on curcumin and curcuminoids. XXIX. Photoinduced cytotoxicity of curcumin in selected aqueous preparations.

Natural curcumin was evaluated as a potential photosensitizer for oral applications. The photocytotoxicity of curcumin on salivary gland acinar cells (SM 10-12) was investigated in five aqueous preparations consisting of 5% DMSO, non-ionic micelles, cyclodextrin, liposomes, or a hydrophilic polymer. The difference in phototoxic effects between natural curcumin and synthetic curcumin was examined. Cytotoxicity in SM 10-12 cells exposed to curcumin in the concentration range 0.4-13.5 microM was investigated by MTT test, a fluorescence-staining microscopic test, and by Western immunoblotting techniques. The potential formation of a photoreaction product, hydrogen peroxide, was evaluated by a fluorescence assay. The light source was a halogen lamp used in the dental clinic, emitting mainly in the blue part of the spectrum. The phototoxic effect on SM 10-12 cells was dependent on curcumin concentration, the light dose and the type of preparation. Natural and synthetic curcumin induced phototoxicity to the same extent. Significant effects on the cells were obtained at low curcumin concentrations (< or =0.5 microM) and at a low light dose (< or =6 J cm(-2)), after 3 h incubation. Neither the activation of caspases-3, -7, -8 or -9, nor the formation of hydrogen peroxide could be detected in cells exposed to curcumin and light. The liposome preparation was the most efficient vehicle for curcumin to induce cell death. The phototoxic effect induced by curcumin is highly dependent on the type of preparation. Curcumin might be a potential photosensitizer in the treatment of oral lesions and cancers provided careful selection of the vehicle.     

Studies on methods for determining varietal utilization of nutrients

Summary In pot experiments with a phosphorus-deficient soil and four barley varieties, Kenia, Maja, Bonus, and Pallas, receiving increasing amounts of phosphorus, it was found that the order of susceptibility to phosphorus deficiency of the varieties was the same for grain as for grain + straw, when the ranking was based on the percentage decrease in dry matter yield as a result of phosphorus deficiency based on the maximum obtained dry matter yield. Estimations of the maximum phosphorus utilization quotients of dry matter yield of grain + straw graduated the susceptibility to phosphorus deficiency of the varieties in the same order.     

Polyploidisierung in der Fischfamilie Cyprinidae,Ordnung Cypriniformes

Zusammenfassung Die Fischfamilie der Cypriniden zeigt nach Chromosomenzahl und DNS-Gehalt/Zelle ein Diploid-Tetraploid-Verhältnis. Eine Duplikation der MDH-Isoenzyme läßt sich in der tetraploiden Gruppe nachweisen. Nur der tetraploide Cyprinus carpio hat ein Muster entsprechend der diploiden Gruppe.

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Polyploidization in the fish family Cyprinidae Duplication of the gene loci for NAD-dependent malate dehydrogenase

Summary The fish family Cyprinidae can be classified into two groups, a diploid one and a tetraploid one, as shown by chromosome analysis and measurements of the DNA content per cell. Duplications of the MDH isoenzymes can be demonstrated in the tetraploid group with one exception: Cyprinus carpio reveals the diploid pattern.

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Direktor: Prof. Dr. Dr. H. Ritter

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Mit Unterstützung durch die Deutsche Forschungsgemeinschaft.