Sphingosine in apoptosis signaling

The sphingolipid metabolites ceramide, sphingosine, and sphingosine 1-phosphate contribute to controlling cell proliferation and apoptosis. Ceramide and its catabolite sphingosine act as negative regulators of cell proliferation and promote apoptosis. Conversely, sphingosine 1-phosphate, formed by phosphorylation of sphingosine by a sphingosine kinase, has been involved in stimulating cell growth and inhibiting apoptosis. As the phosphorylation of sphingosine diminishes apoptosis, while dephosphorylation of sphingosine 1-phosphate potentiates it, the role of sphingosine as a messenger of apoptosis is of importance. Herein, the effects of sphingosine on diverse signaling pathways implicated in the apoptotic process are reviewed.     

Advanced glycation end-products disrupt human endothelial cells redox homeostasis: new insights into reactive oxygen species production

Advanced glycation end-products (AGEs) trigger multiple metabolic disorders in the vessel wall that may in turn lead to endothelial dysfunction. The molecular mechanisms by which AGEs generate these effects are not completely understood. Oxidative stress plays a key role in the development of deleterious effects that occur in endothelium during diabetes. Our main objectives were to further understand how AGEs contribute to reactive oxygen species (ROS) overproduction in endothelial cells and to evaluate the protective effect of an antioxidant plant extract. The human endothelial cell line EA.hy926 was treated with native or modified bovine serum albumin (respectively BSA and BSA-AGEs). To monitor free radicals formation, we used H₂DCF-DA, dihydroethidium (DHE), DAF-FM-DA and MitoSOX Red dyes. To investigate potential sources of ROS, nicotinamide adenine dinucleotide phosphate (NADPH) oxidase and mitochondrial inhibitors were used. The regulation of different types of ROS by the polyphenol-rich extract from the medicinal plant Doratoxylon apetalum was also studied for a therapeutic perspective. BSA-AGEs exhibited not only less antioxidant properties than BSA, but also pro-oxidant effects. The degree of albumin glycoxidation directly influenced oxidative stress through a possible communication between NADPH oxidase and mitochondria. D. apetalum significantly decreased intracellular hydrogen peroxide and superoxide anions mainly detected by H₂DCF-DA and DHE respectively. Our results suggest that BSA-AGEs promote a marked oxidative stress mediated at least by NADPH oxidase and mitochondria. D. apetalum plant extract appeared to be an effective antioxidant compound to protect endothelial cells.     

Crystal structure of Zn(trz)Cl (trz = 11,2,4,-triazolato); a layered compound with triply bridging triazolato groups

ZnCl₂ reacts with 1,2,4-1H-triazole to afford Zn(trz)Cl. A spontaneous deprotonation of Htrz occurs. The crystal structure of Zn(trz)Cl has been solved. The compound crystallizes in the space group P2₁/n. The lattice parameters are a = 8.863(4), B = 9.762(4), C = 6.146(3) Å, β = 99.56(10)°, with Z = 4. The 1,2,4-triazolato bridges three zinc atoms through its three nitrogen atoms, affording a layered structure. The zinc atom is in an N₃Cl tetrahedral coordination. The layers are not planar, but rather corrugated. The chlorine atoms point to either side of the layers, and play the role of spacers. The shortest interlayer ZnZn separation is 5.701 Å.     

The Farnesoid X Receptor Regulates Adipocyte Differentiation and Function by Promoting Peroxisome Proliferator-activated Receptor-γ and Interfering with the Wnt/β-Catenin Pathways

The bile acid receptor farnesoid X receptor (FXR) is expressed in adipose tissue, but its function remains poorly defined. Peroxisome proliferator-activated receptor-γ (PPARγ) is a master regulator of adipocyte differentiation and function. The aim of this study was to analyze the role of FXR in adipocyte function and to assess whether it modulates PPARγ action. Therefore, we tested the responsiveness of FXR-deficient mice (FXR^−/−) and cells to the PPARγ activator rosiglitazone. Our results show that genetically obese FXR^−/−/ob/ob mice displayed a resistance to rosiglitazone treatment. In vitro, rosiglitazone treatment did not induce normal adipocyte differentiation and lipid droplet formation in FXR^−/− mouse embryonic fibroblasts (MEFs) and preadipocytes. Moreover, FXR^−/− MEFs displayed both an increased lipolysis and a decreased de novo lipogenesis, resulting in reduced intracellular triglyceride content, even upon PPARγ activation. Retroviral-mediated FXR re-expression in FXR^−/− MEFs restored the induction of adipogenic marker genes during rosiglitazone-forced adipocyte differentiation. The expression of Wnt/β-catenin pathway and target genes was increased in FXR^−/− adipose tissue and MEFs. Moreover, the expression of several endogenous inhibitors of this pathway was decreased early during the adipocyte differentiation of FXR^−/− MEFs. These findings demonstrate that FXR regulates adipocyte differentiation and function by regulating two counteracting pathways of adipocyte differentiation, the PPARγ and Wnt/β-catenin pathways.     

Identifying climatic niche shifts using coarse‐grained occurrence data: a test with non‐native freshwater fish

Aim We tested whether coarse‐grained occurrence data can be used to detect climatic niche shifts between native and non‐native ranges for a set of widely introduced freshwater fishes. Location World‐wide. Methods We used a global database of freshwater fish occurrences at the river basin scale to identify native and non‐native ranges for 18 of the most widely introduced fish species. We also examined climatic conditions within each river basin using fine‐grained climate data. We combined this information to test whether climatic niche shifts have occurred between native and non‐native ranges. We defined climatic niche shifts as instances where the ranges of a climatic variable within native and non‐native basins exhibit zero overlap. Results We detected at least one climatic niche shift for each of the 18 studied species. However, we did not detect common patterns in the thermal preference or biogeographic origin of the non‐native fish, hence suggesting a species‐specific response. Main conclusions Coarse‐grained occurrence data can be used to detect climatic niche shifts. They also enable the identification of the species experiencing niche shifts, although the mechanisms responsible for these shifts (e.g. local adaptation, dispersal limitation or physiological constraints) have yet to be determined. Furthermore, the coarse‐grained approach, which highlights regions where climatic niche shifts have occurred, can be used to select specific river basins for more detailed, fine‐grained studies.