4 results on '"Yang, Silei"'
Search Results
2. Non-receptor-tyrosine kinases integrate fast glucocorticoid signaling in hippocampal neurons.
- Author
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Yang S, Roselli F, Patchev AV, Yu S, and Almeida OF
- Subjects
- Actins metabolism, Animals, Cell Membrane drug effects, Cell Membrane metabolism, Corticosterone pharmacology, Enzyme Activation drug effects, GTP-Binding Proteins metabolism, Models, Biological, Neurons drug effects, Phosphorylation drug effects, Rats, Receptors, G-Protein-Coupled metabolism, Receptors, N-Methyl-D-Aspartate metabolism, Glucocorticoids metabolism, Hippocampus cytology, Neurons enzymology, Receptor Protein-Tyrosine Kinases metabolism, Signal Transduction drug effects
- Abstract
Despite numerous descriptions of rapid effects of corticosterone on neuronal function, the intracellular mechanisms responsible for these changes remain elusive. The present comprehensive analysis reveals that signaling from a membrane-located G protein-coupled receptor activates PKC, Akt/PKB, and PKA, which subsequently trigger the phosphorylation of the tyrosine kinases Pyk2, Src, and Abl. These changes induce rapid cytoskeletal rearrangements (increased PSD-95 co-clustering) within the post-synaptic density; these events are accompanied by increased surface NMDA receptor expression, reflecting corticosterone-induced inhibition of NMDA receptor endocytosis. Notably, none of these signaling mechanisms require de novo protein synthesis. The observed up-regulation of ERK1/2 (downstream of NMDA receptor signaling) together with the fact that c-Abl integrates cytoplasmic and nuclear functions introduces a potential mechanism through which rapid signaling initiated at the plasma membrane may eventually determine the long term integrated response to corticosterone by impacting on the transcriptional machinery that is regulated by classical, nuclear mineralocorticoid, and glucocorticoid receptors.
- Published
- 2013
- Full Text
- View/download PDF
3. Glucocorticoid regulation of astrocytic fate and function.
- Author
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Yu S, Yang S, Holsboer F, Sousa N, and Almeida OF
- Subjects
- Aging drug effects, Animals, Animals, Newborn, Apoptosis drug effects, Astrocytes drug effects, Astrocytes enzymology, Caspase 3 metabolism, Cell Proliferation drug effects, Cells, Cultured, Culture Media, Conditioned pharmacology, Cytokines metabolism, Enzyme Activation drug effects, Gene Expression Profiling, Gene Expression Regulation, Developmental drug effects, Hippocampus cytology, Neurogenesis drug effects, Neurons cytology, Neurons drug effects, Neurons metabolism, Phenotype, RNA, Messenger genetics, RNA, Messenger metabolism, Rats, Receptors, Glucocorticoid metabolism, Astrocytes cytology, Astrocytes metabolism, Cell Lineage drug effects, Glucocorticoids pharmacology
- Abstract
Glial loss in the hippocampus has been suggested as a factor in the pathogenesis of stress-related brain disorders that are characterized by dysregulated glucocorticoid (GC) secretion. However, little is known about the regulation of astrocytic fate by GC. Here, we show that astrocytes derived from the rat hippocampus undergo growth inhibition and display moderate activation of caspase 3 after exposure to GC. Importantly, the latter event, observed both in situ and in primary astrocytic cultures is not followed by either early- or late-stage apoptosis, as monitored by stage I or stage II DNA fragmentation. Thus, unlike hippocampal granule neurons, astrocytes are resistant to GC-induced apoptosis; this resistance is due to lower production of reactive oxygen species (ROS) and a greater buffering capacity against the cytotoxic actions of ROS. We also show that GC influence hippocampal cell fate by inducing the expression of astrocyte-derived growth factors implicated in the control of neural precursor cell proliferation. Together, our results suggest that GC instigate a hitherto unknown dialog between astrocytes and neural progenitors, adding a new facet to understanding how GC influence the cytoarchitecture of the hippocampus.
- Published
- 2011
- Full Text
- View/download PDF
4. TIP30 inhibits growth of HCC cell lines and inhibits HCC xenografts in mice in combination with 5-FU.
- Author
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Zhao J, Zhang X, Shi M, Xu H, Jin J, Ni H, Yang S, Dai J, Wu M, and Guo Y
- Subjects
- Acetyltransferases genetics, Adenoviridae, Animals, Apoptosis, Blotting, Western, Carcinogenicity Tests, Carcinoma, Hepatocellular drug therapy, Cell Line, Tumor, DNA, Neoplasm genetics, Flow Cytometry, Gene Expression Regulation, Neoplastic, Genetic Vectors, Humans, Immunohistochemistry, In Vitro Techniques, Liver Neoplasms drug therapy, Mice, Mice, Nude, Neoplasm Transplantation, Transcription Factors genetics, Transplantation, Heterologous, Treatment Outcome, Acetyltransferases pharmacology, Antimetabolites, Antineoplastic pharmacology, Carcinoma, Hepatocellular pathology, Cell Proliferation drug effects, Fluorouracil pharmacology, Liver Neoplasms pathology, Transcription Factors pharmacology
- Abstract
Hepatocellular carcinoma (HCC) is an aggressive cancer with a poor prognosis. The specific cellular gene alterations responsible for hepatocarcinogenesis are not well known. Previous works showed that loss of TIP30, also called CC3, a putative tumor suppressor, increased the incidence of hepatocellular carcinoma in mice, and some clinical samples of human HCC tissues had aberrant expression of TIP30. Here, we report that the introduction of TIP30 by an adenovirus vector into HCC cell lines that had decreased expressions of TIP30 inhibited cell proliferation, decreased anchorage-dependent growth, suppressed invasion through the extracellular matrix, and inhibited tumorigenesis in nude mice. Moreover, exogenous expression of Tip30 sensitized HCC cells to cytotoxic drugs and to apoptosis induced by tumor necrosis factor-related ligands in vitro. Ectopic expression of TIP30 in HCC cells enhanced p53 expression and decreased Bcl-2/Bcl-xL expression. Treatment of nude mice bearing subcutaneously established HCC tumors with a combination of an adenovirus expressing TIP30 and the cytotoxic drug 5-fluorouracil completely suppressed tumor growth and prolonged survival. In conclusion, TIP30 may play an important role in the suppression of hepatocarcinogenesis by acting as a tumor suppressor. Overexpression of TIP30 might be a promising candidate as a treatment for HCC that would increase sensitivity to chemotherapeutic drugs.
- Published
- 2006
- Full Text
- View/download PDF
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