Mouse aortic muscle cells respond to oxygen following cytochrome P450 3A13 gene transfer

We have previously shown that a cytochrome P450 (CYP450) hemoprotein from the 3A subfamily CYP3A13 for the mouse, serves as the sensor in the contraction of the ductus arteriosus in response to increased oxygen tension. In addition, we have identified endothelin-1 (ET-1) as the effector for this response. Here, we examined whether Cyp3a13 gene transfer confers oxygen sensitivity to cultured muscle cells from mouse aorta. Coincidentally, we determined whether the same hemoprotein is normally present in the vessel. Cyp3a13-transfected aortic cells responded to oxygen, whereas no significant response was seen in native cells or in cells transfected with an empty vector. Furthermore, this oxygen effect was curtailed by the ET-1/ETA receptor antagonist BQ-123. We also found that CYP3A13 occurs naturally in aortic tissue and its isolated muscle cells in culture. We conclude that CYP3A13 is involved in oxygen sensing, and its action in the transfected muscle cells of the aorta, as in the native cells of the ductus, takes place through a linkage to ET-1. However, the response of aortic muscle to oxygen, conceivably entailing the presence of CYP3A13 at some special site, is not seen in the native situation, and may instead unfold upon transfection of the parent gene

A SELDI-TOF approach to ecotoxicology: Comparative profiling of low molecular weight proteins from a marine diatom exposed to CdSe/ZnS quantum dots

Quantum dots (QDs), namely semiconductor nanocrystals, due to their particular optical and electronic properties, have growing applications in device technology, biotechnology and biomedical fields. Nevertheless, the possible threat to human health and the environment have attracted increasing attention as the production and applications of QDs increases rapidly while standard evaluation of safety lags. In the present study we performed proteomic analyses, by means of 2D gel electrophoresis and Surface Enhanced Laser Desorption Ionization-Time of Flight-Mass Spectrometry (SELDI-TOF-MS). We aimed to identify potential biomarkers of exposure to CdSe/ZnS quantum dots. The marine diatom Phaeodactylum tricornutum exposed to 2.5nM QDs was used as a model system. Both 2DE and SELDI showed the presence of differentially expressed proteins. By Principal Component Analysis (PCA) we were able to show that the differentially expressed proteins can discriminate between exposed and not exposed cells. Furthermore, a protein profile specific for exposed cells was obtained by SELDI analysis. To our knowledge, this is the first example of the application of SELDI technology to the analysis of microorganisms used as biological sentinel model of marine environmental pollution

Melatonin MT1 receptors as a target for the psychopharmacology of bipolar disorder: a translational study

The treatment of bipolar disorder (BD) still remains a challenge. Melatonin (MLT), acting through its two receptors MT1 and MT2, plays a key role in regulating circadian rhythms which are dysfunctional in BD. Using a translational approach, we examined the implication and potential of MT1 receptors in the pathophysiology and psychopharmacology of BD. We employed a murine model of the manic phase of BD (Clock mutant (ClockΔ19) mice) to study the activation of MT1 receptors by UCM871, a selective partial agonist, in behavioral pharmacology tests and in-vivo electrophysiology. We then performed a high-resolution Nuclear Magnetic Resonance study on isolated membranes to characterize the molecular mechanism of interaction of UCM871. Finally, in a cohort of BD patients, we investigated the link between clinical measures of BD and genetic variants located in the MT1 receptor and CLOCK genes. We demonstrated that: 1) UCM871 can revert behavioral and electrophysiological abnormalities of ClockΔ19 mice; 2) UCM871 promotes the activation state of MT1 receptors; 3) there is a significant association between the number of severe manic episodes and MLT levels, depending on the genetic configuration of the MT1 rs2165666 variant. Overall, this work lends support to the potentiality of MT1 receptors as target for the treatment of BD

Heavy metal accumulation and growth responses in poplar clones Eridano (Populus deltoides x maximowiczii) and I-214 (P. x euramericana) exposed to industrial waste

In this study, the effects of non-hazardous levels of heavy metal (Zn, Cu, Cr and Cd)-enriched organic waste on biomass partitioning and heavy metal accumulation in plant organs in July and October were determined for two poplar clones (Populus deltoides × maximowiczii—clone Eridano and P. × euramericana—clone I-214) commonly used in Italian poplar plantations. Soil amended with the industrial organic waste did not exert any toxic effects on plants. Leaf, stem, root and woody cutting biomasses of treated plants were significantly greater than in the controls in both clones, except for stem biomass at the beginning of October. Leaf area of Eridano and I-124 treated plants was significantly higher than that of control plants, both in July and October, while specific leaf area (SLA) did not show any significant changes due to treatment. Shoot (SMR) and root mass ratios (RMR) were not significantly affected by the treatment in July, while in October plants grown in treated soil showed significant differences in stem and root biomass allocation with respect to controls. Among the four heavy metals (Zn, Cu, Cr and Cd) contained in the industrial organic waste, only Zn, Cu and Cr concentrations in plants differed consistently between clones or soil treatments, while Cd levels were always below the detection limits. Both phytoextraction and phytostabilisation strategies were observed in the two clones studied. The results suggested that only non-hazardous industrial biosolid levels might be environmentally sustainable for poplar plantations