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Start Over Author "Reinhardt B" Topic apoptosis
3 results on '"Reinhardt B"'

1. Apoptosis and differentiation commitment: novel insights revealed by gene profiling studies in mouse embryonic stem cells.

Author

Duval D, Trouillas M, Thibault C, Dembelé D, Diemunsch F, Reinhardt B, Mertz AL, Dierich A, and Boeuf H

Subjects
Animals, Cell Line, Embryo, Mammalian cytology, Enzyme Inhibitors pharmacology, Gene Expression Profiling, Gene Expression Regulation, Developmental drug effects, Imidazoles pharmacology, Interleukin-6 pharmacology, Leukemia Inhibitory Factor, Metallothionein genetics, Metallothionein metabolism, Mice, Pluripotent Stem Cells cytology, Pluripotent Stem Cells drug effects, Pluripotent Stem Cells enzymology, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Stem Cells drug effects, Stem Cells enzymology, Transfection, p38 Mitogen-Activated Protein Kinases metabolism, Apoptosis genetics, Cell Differentiation genetics, Stem Cells cytology, p38 Mitogen-Activated Protein Kinases antagonists & inhibitors
Abstract

Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in the presence of leukemia inhibitory factor (LIF). LIF starvation leads to apoptosis of some of the ES-derived differentiated cells, together with p38alpha mitogen-activated protein kinase (MAPK) activation. Apoptosis, but not morphological cell differentiation, is blocked by a p38 inhibitor, PD169316. To further understand the mechanism of action of this compound, we have identified its specific targets by microarray studies. We report on the global expression profiles of genes expressed at 3 days upon LIF withdrawal (d3) compared to pluripotent cells and of genes whose expression is modulated at d3 under anti-apoptotic conditions. We showed that at d3 without LIF cells express, earlier than anticipated, specialized cell markers and that when the apoptotic process was impaired, expression of differentiation markers was altered. In addition, functional tests revealed properties of anti-apoptotic proteins not to alter cell pluripotency and a novel role for metallothionein 1 gene, which prevents apoptosis of early differentiated cells.

Published
2006
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2. A p38 inhibitor allows to dissociate differentiation and apoptotic processes triggered upon LIF withdrawal in mouse embryonic stem cells.

Author

Duval D, Malaisé M, Reinhardt B, Kedinger C, and Boeuf H

Subjects
Animals, Blotting, Western, Caspases drug effects, Caspases metabolism, Cell Survival drug effects, Cells, Cultured, Clone Cells, Culture Media, Enzyme Activation, Enzyme Inhibitors pharmacology, Flow Cytometry, Gene Expression Profiling, Gene Expression Regulation drug effects, Green Fluorescent Proteins, Imidazoles pharmacology, Interleukin-6, Leukemia Inhibitory Factor, Luminescent Proteins metabolism, Mice, Mitogen-Activated Protein Kinases antagonists & inhibitors, Mitogen-Activated Protein Kinases deficiency, Mitogen-Activated Protein Kinases genetics, Mitogen-Activated Protein Kinases metabolism, Models, Biological, Proto-Oncogene Proteins c-bcl-2 genetics, Proto-Oncogene Proteins c-bcl-2 metabolism, Pyridines pharmacology, Recombinant Fusion Proteins metabolism, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells metabolism, Apoptosis, Cell Differentiation, Mitogen-Activated Protein Kinases drug effects, Stem Cells cytology, Stem Cells drug effects
Abstract

Mouse embryonic stem cells remain pluripotent when maintained in the presence of leukemia inhibitory factor (LIF). Upon LIF withdrawal, most cells differentiate into various lineages, while some die by apoptosis within 3 days. We have analyzed the activation pattern of the mitogen-activated protein kinase (MAPK) families and characterized the expression profile of selected genes modulated during differentiation or apoptosis. We show that p38 MAPKs are activated first, during the apoptotic crisis, while extracellular-regulated kinases and c-Jun N-terminal kinases are induced after the apoptotic crisis in differentiated cells. However, by using both p38 kinase inhibitors (PD169316 and SB203580) and a p38alpha(-/-) cell line, we demonstrate that p38alpha activation is rather a consequence than a cause of apoptosis. We thus reveal novel properties of PD169316, which induces cell survival without impairing cell differentiation, and identify PD169316-sensitive targets like the fibroblast growth factor-5, Brachyury and bcl-2 genes. Finally, we demonstrate that overexpression of the PD169316 - regulated bcl-2 gene prevents LIF withdrawal - induced cell death.

Published
2004
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3. Role of suppressors of cytokine signaling (Socs) in leukemia inhibitory factor (LIF) -dependent embryonic stem cell survival

Author

David Duval, Reinhardt, B., Kedinger, C., and Boeuf, H.

Subjects
Transcription, Genetic, Cell Survival, Apoptosis, Suppressor of Cytokine Signaling Proteins, Transfection, Biochemistry, Leukemia Inhibitory Factor, Cell Line, Mice, Suppressor of Cytokine Signaling 1 Protein, Genes, jun, Genetics, Animals, RNA, Messenger, Molecular Biology, Lymphokines, Interleukin-6, Reverse Transcriptase Polymerase Chain Reaction, Stem Cells, Genes, fos, Proteins, Cell Differentiation, Growth Inhibitors, DNA-Binding Proteins, Repressor Proteins, Gene Expression Regulation, Suppressor of Cytokine Signaling 3 Protein, Trans-Activators, Carrier Proteins, Biotechnology, Signal Transduction, Transcription Factors
Abstract

Mouse embryonic stem (ES) cells remain pluripotent in vitro when grown in the presence of leukemia inhibitory factor (LIF). LIF withdrawal results in progressive ES cell differentiation. Here we show that during this differentiation process, part of the cells undergo apoptosis concomitant with an activation of the p38 MAP kinase. To gain insight into events mediated by LIF in ES cells, the expression of potential candidate genes was analyzed in the absence or presence of this cytokine by using a semiquantitative RT-PCR assay. We focused on early response genes and on a new type of cytokine repressors (the Socs proteins), some of which exhibit anti-apoptotic properties. We found that expression of c-Fos, c-Jun, and JunB was induced upon LIF treatment whereas that of JunD, the tyrosine phosphatase ESP, and the components of the LIF receptor remained unaffected. Expression of Socs-3, but not Socs-1 or Socs-2, was stimulated in the presence of LIF. Finally, uncontrolled overexpression of Socs-1 and Socs-3 led to repression of LIF-dependent transcription and severely reduced cell viability, suggesting that the disturbance of a well balanced Socs protein content has adverse effects on cell survival.

Published
2000

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