Effect of synthetic enantiomeric cannabinoids on platelet aggregation.

The effect of a synthetic pair of enantiomeric cannabinoids on platelet function was evaluated. The nonpsychotropic enantiomer, the 1,1-dimethylheptyl homolog of (+)-(3S,4S)-7-hydroxy-delta-6-tetrahydrocannabinol (HU-211), was found to be more active in inhibiting ADP-induced platelet aggregation than the highly psychotropic (-)-enantiomer (HU-210). The related (+)-(3R,4R) cannabinoid, HU-213, which lacks the 7-hydroxy moiety, exerted its inhibitory effect within a wider range of concentrations. The results indicate a differentiation between psychotropic activity and inhibition of platelet aggregation in the cannabinoid group of compounds.     

Dual Neuroprotective and Neurotoxic Effects of Cannabinoid Drugs in Vitro

Either protective or toxic effects of cannabinoids on cell survival have been reported extensively in the literature; however, the factors that determine the direction of the effect are still obscured. In this study we have used the neuroblastoma cell line N18TG2 that expresses CB1 cannabinoid receptors to investigate several factors that may determine the consequences of exposure to cannabinoid agonists. Cells that were grown under optimal, stressful, or differentiating conditions were exposed to cannabinoid agonists and then assayed for cell viability by measuring MTT, LDH, and caspase-3 activity. Various cannabinoid agonists (CP 55,940, ∆9-THC, HU-210, and WIN 55,212-2) failed to affect cell viability when the cells were grown under optimal conditions. On the other hand, the same agonists significantly reduced cell viability when the cells were grown under stressful conditions (glucose- and serum-free medium), while enhancing the viability of cells grown in differentiation medium (0.5% serum and 1.5% DMSO). The toxic/protective profile was not dependent on the type or the concentration of the cannabinoid agonist that was applied. The cannabinoid agonist CP 55,940 similarly affected the non-neuronal HEK-293 cells that were grown under stressful conditions only when they expressed CB1 receptors. Our results shed light on the conflicting reports regarding the protective or toxic effects of cannabinoids in vitro and indicate that cannabinoids may activate different intracellular signaling mechanisms, depending on the state of the cell, thus leading to different physiological consequences.     

大鼠尾壳核头部生长抑素mRNA的区域性表达

目的　观察尾壳核 (CP)头部背内侧区、背外侧区、腹内侧区和腹外侧区生长抑素 (SOM )mRNA阳性神经元分布特点。方法　采用原位杂交组织化学方法。结果　CP头部不同区域SOMmRNA阳性神经元的密度存在差异 ,腹内侧区SOMmRNA阳性神经元的密度明显高于其他区 (P <0 0 1)。结论　CP头部不同区域的SOMmRNA阳性神经元密度存在差异 ,这可能是CP头部不同区域机能差异的形态学基础之一。     

Similar cation channels mediate protection from cerebellar exitotoxicity by exercise and inheritance

Exercise and inherited factors both affect recovery from stroke and head injury, but the underlying mechanisms and interconnections between them are yet unknown. Here, we report that similar cation channels mediate the protective effect of exercise and specific genetic background in a kainate injection model of cerebellar stroke. Microinjection to the cerebellum of the glutamatergic agonist, kainate, creates glutamatergic excito\xE2\x80\x90toxicity characteristic of focal stroke, head injury or alcoholism. Inherited protection and prior exercise were both accompanied by higher cerebellar expression levels of the Kir6.1 ATP-dependent potassium channel in adjacent Bergmann glia, and voltage-gated KVbeta2 and cyclic nucleotide-gated cation HCN1 channels in basket cells. Sedentary FVB/N and exercised C57BL/6 mice both expressed higher levels of these cation channels compared to sedentary C57BL/6 mice, and were both found to be less sensitive to glutamate toxicity. Moreover, blocking ATP-dependent potassium channels with Glibenclamide enhanced kainate-induced cell death in cerebellar slices from the resilient sedentary FVB/N mice. Furthermore, exercise increased the number of acetylcholinesterase-positive fibres in the molecular layer, reduced cerebellar cytokine levels and suppressed serum acetylcholinesterase activity, suggesting anti-inflammatory protection by enhanced cholinergic signalling. Our findings demonstrate for the first time that routine exercise and specific genetic backgrounds confer protection from cerebellar glutamatergic damages by similar molecular mechanisms, including elevated expression of cation channels. In addition, our findings highlight the involvement of the cholinergic anti-inflammatory pathway in insult-inducible cerebellar processes. These mechanisms are likely to play similar roles in other brain regions and injuries as well, opening new venues for targeted research efforts.     

Selective binding of concanavalin A to target cell major histocompatibility antigens is required to induce nonspecific conjugation and lysis by cytolytic T lymphocytes in lectin-dependent cytotoxicity

The exquisite immunological specificity of cytotoxic T lymphocytes-target cell (CTL-TC) conjugation and lysis is overridden in the presence of certain plant lectins. The role of concanavalin A (Con A) in lectin-dependent, CTL-mediated cytolysis (LDCC) has been investigated. Papain-treated TC are refractory to LDCC, but regain susceptibility following a 3-hr incubation without the enzyme. Papain-treated TC allowed to recover in the presence of tunicamycin (TM; an inhibitor of N-linked glycosylation), are totally refractory to LDCC. Refractoriness of TM-treated TC to LDCC is not due to an overall resistance to lysis or to lack of Con A binding, as these cells can be lysed by specifically sensitized CTL or by H-2 antibody and complement and display a sufficiently high Con A-binding capacity, indistinguishable from intact TC, probably through O-linked, cell-surface glycosyl residues. The finding that TC (TM-treated) capable of binding normal Con A quantities cannot, however, engage in lectin-dependent CTL-TC conjugation and lysis indicates that Con A must react selectively with a specific TC-surface component(s), thereby rendering the TC recognizable by effector CTL, rather than by simply bridging ("glueing") CTL and TC. Affinity absorption and elution from Sepharose-Con A beads as well as specific immunoprecipitations by antibodies against cell surface determinants, have shown effective Con A binding to TC surface components of molecular weights corresponding to 45-kDa product of the H-2K and D MHC genes and, possibly, to a 30-kDa component. Antibodies against MHC proteins but not against non-MHC surface proteins of the TC have produced effective inhibition of LDCC. This and previous investigations show that in nonspecific LDCC as in specific CTL-mediated lysis, TC-MHC determinants are involved in signaling TC recognition and lysis.     

Expression profiles of microRNAs in oxidized low-density lipoprotein-stimulated RAW 264.7 cells

Macrophage-derived foam cells were one of the hallmarks of atherosclerosis, and microRNAs played an important role in the formation of foam cells. In order to explore the roles of miRNA in the formation of foam cells, we investigated miRNA expression profiles in foam cells through high-throughput sequencing technology. A total of 84 miRNAs were differentially expressed between RAW 264.7 macrophages and foam cells induced by ox-LDL. Thirty miRNAs were upregulated and 54 miRNAs were downregulated. GO terms and KEGG pathways analysis revealed that the target genes of most of DE miRNAs were mainly enriched in “cell differentiation,” “endocytosis,” “MAPK signaling pathway,” and “FoxO signaling pathway.” The target genes of some DE miRNAs were enriched in “Insulin signaling pathway,” “Hippo signaling pathway,” “TNF signaling pathway,” “NF-kappa B signaling pathway,” and “cell death.” Using bioinformatics analyses and dual-luciferase reporter assays, we found that miR-28a-5p and miR-30c-1-3p directly inhibited LRAD3 and LOX-1 mRNA expression through targeting the 3’UTR of LRAD3 and LOX-1 mRNA, respectively. Our study indicates that miRNAs are extensively involved in the formation of foam cells, and provides a valuable resource for further study the role of miRNAs in atherosclerosis.     

Function of the IsiA pigment–protein complex in vivo

Photosynthesis Research - The acclimation of cyanobacterial photosynthetic apparatus to iron deficiency is crucial for their performance under limiting conditions. In many cyanobacterial species,...     

Psb29, a conserved 22-kD protein, functions in the biogenesis of Photosystem II complexes in Synechocystis and Arabidopsis

Photosystem II (PSII), the enzyme responsible for photosynthetic oxygen evolution, is a rapidly turned over membrane protein complex. However, the factors that regulate biogenesis of PSII are poorly defined. Previous proteomic analysis of the PSII preparations from the cyanobacterium Synechocystis sp PCC 6803 detected a novel protein, Psb29 (Sll1414), homologs of which are found in all cyanobacteria and vascular plants with sequenced genomes. Deletion of psb29 in Synechocystis 6803 results in slower growth rates under high light intensities, increased light sensitivity, and lower PSII efficiency, without affecting the PSII core electron transfer activities. A T-DNA insertion line in the PSB29 gene in Arabidopsis thaliana displays a phenotype similar to that of the Synechocystis mutant. This plant mutant grows slowly and exhibits variegated leaves, and its PSII activity is light sensitive. Low temperature fluorescence emission spectroscopy of both cyanobacterial and plant mutants shows an increase in the proportion of uncoupled proximal antennae in PSII as a function of increasing growth light intensities. The similar phenotypes observed in both plant and cyanobacterial mutants demonstrate that the function of Psb29 has been conserved throughout the evolution of oxygenic photosynthetic organisms and suggest a role for the Psb29 protein in the biogenesis of PSII.