Euphorbiasteroid,a component of Euphorbia lathyris L., inhibits adipogenesis of 3T3‐L1 cells via activation of AMP‐activated protein kinase

The purpose of this study is to investigate the effects of euphorbiasteroid, a component of Euphorbia lathyris L., on adipogenesis of 3T3‐L1 pre‐adipocytes and its underlying mechanisms. Euphorbiasteroid decreased differentiation of 3T3‐L1 cells via reduction of intracellular triglyceride (TG) accumulation at concentrations of 25 and 50 μM. In addition, euphorbiasteroid altered the key regulator proteins of adipogenesis in the early stage of adipocyte differentiation by increasing the phosphorylation of AMP‐activated protein kinase (AMPK) and acetyl‐CoA carboxylase. Subsequently, levels of adipogenic proteins, including fatty acid synthase, peroxisome proliferator‐activated receptor‐γ and CCAAT/enhancer‐binding protein α, were decreased by euphorbiasteroid treatment at the late stage of adipocyte differentiation. The anti‐adipogenic effect of euphorbiasteroid may be derived from inhibition of early stage of adipocyte differentiation. Taken together, euphorbiasteroid inhibits adipogenesis of 3T3‐L1 cells through activation of the AMPK pathway. Therefore, euphorbiasteroid and its source plant, E. lathyris L., could possibly be one of the fascinating anti‐obesity agent. Copyright © 2015 John Wiley & Sons, Ltd.     

Embryonic Stem Cell-Derived Extracellular Vesicles Maintain ESC Stemness by Activating FAK

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The combination of berberine and irradiation enhances anti‐cancer effects via activation of p38 MAPK pathway and ROS generation in human hepatoma cells

Berberine, an isoquinoline plant alkaloid, has been known to generate a wide variety of biochemical and pharmacological effects. In order to elucidate the molecular mechanism for the berberine‐induced enhancement of radio‐sensitization, the human hepatoma HepG2 cells were treated with berberine combined with irradiation. The anti‐tumor effect of gamma radiation was found to be significantly enhanced by berberine. The evidences of apoptosis, such as apoptotic DNA fragmentation and annexin V staining, were observed in the cells treated with the combination of berberine and irradiation. Additionally, the levels of reactive oxygen species (ROS) and nitric oxide (NO) were apparently elevated in the combination system. The activations of p38, Bax, and caspase‐3 were also detected in the irradiated cells pretreated with berberine. The productions of ROS and annexin V staining in the cells treated with the combination of berberine and irradiation were significantly inhibited by the specific inhibitor of p38 MAPK, SB203580. The cell death induced by berberine alone or the combination of berberine and irradiation was suppressed by the anti‐oxidant, N‐acetyl cysteine (NAC). Taken together, the present results clearly indicate that the combination of berberine and gamma‐radiation enhance the anti‐cancer effects through the p38 MAPK pathway and ROS generation. J. Cell. Biochem. 107: 955–964, 2009. © 2009 Wiley‐Liss, Inc.     

Plasma Membrane Localized GCaMP-MS4A12 by Orai1 Co-Expression Shows Thapsigargin- and Ca2+-Dependent Fluorescence Increases

Uniquely expressed in the colon, MS4A12 exhibits store-operated Ca²⁺ entry (SOCE) activity. However, compared to MS4A1 (CD20), a Ca²⁺ channel and ideal target for successful leukaemia immunotherapy, MS4A12 has rarely been studied. In this study, we investigated the involvement of MS4A12 in Ca²⁺ influx and expression changes in MS4A12 in human colonic malignancy. Fluorescence of GCaMP-fused MS4A12 (GCaMP-M12) was evaluated to analyse MS4A12 activity in Ca²⁺ influx. Plasma membrane expression of GCaMP-M12 was achieved by homo- or hetero-complex formation with no-tagged MS4A12 (nt-M12) or Orai1, respectively. GCaMP-M12 fluorescence in plasma membrane increased only after thapsigargin-induced depletion of endoplasmic reticulum Ca²⁺ stores, and this fluorescence was inhibited by typical SOCE inhibitors and siRNA for Orai1. Furthermore, GCaMP-MS4A12 and Orai1 co-transfection elicited greater plasma membrane fluorescence than GCaMP-M12 co-transfected with nt-M12. Interestingly, the fluorescence of GCaMP-M12 was decreased by STIM1 over-expression, while increased by siRNA for STIM1 in the presence of thapsigargin and extracellular Ca²⁺. Moreover, immunoprecipitation assay revealed that Orai1 co-expression decreased protein interactions between MS4A12 and STIM1. In human colon tissue, MS4A12 was expressed in the apical region of the colonic epithelium, although its expression was dramatically decreased in colon cancer tissues. In conclusion, we propose that MS4A12 contributes to SOCE through complex formation with Orai1, but does not cooperate with STIM1. Additionally, we discovered that MS4A12 is expressed in the apical membrane of the colonic epithelium and that its expression is decreased with cancer progression.     

Description of Anaerostipes faecalis sp. nov., a new segmented filamentous bacterium isolated from swine faeces

Antonie van Leeuwenhoek - A novel, strictly anaerobic, gram-negative, segmented filamentous bacterium strain AGMB03513T, was isolated from the faeces of a 5-month-old pig. Phylogenetic analysis...