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2 results on '"Noémie Ravalet"'

1. Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Author

Christine Vignon, Christelle Debeissat, Jérôme Bourgeais, Nathalie Gallay, Farah Kouzi, Adrienne Anginot, Frédéric Picou, Philippe Guardiola, Elfi Ducrocq, Amélie Foucault, Noémie Ravalet, Louis-Romée Le Nail, Jorge Domenech, Marie-Christine Béné, Marie-Caroline Le Bousse-Kerdilès, Emmanuel Gyan, and Olivier Herault

Subjects
leukemic cell, mesenchymal stromal cell, reactive oxygen species, microenvironment, GPx-3, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell–cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.

Published
2020
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2. Involvement of GPx-3 in the Reciprocal Control of Redox Metabolism in the Leukemic Niche

Author

Elfi Ducrocq, Farah Kouzi, Jorge Domenech, Amélie Foucault, Philippe Guardiola, Frederic Picou, Emmanuel Gyan, Marie-Caroline Le Bousse-Kerdilès, Nathalie Gallay, Olivier Herault, Christelle Debeissat, Noémie Ravalet, Adrienne Anginot, Jérôme Bourgeais, Louis-Romée Le Nail, Christine Vignon, and Marie-Christine Béné

Subjects
GPX3, medicine.disease_cause, Catalysis, Gene Expression Regulation, Enzymologic, Article, Inorganic Chemistry, GPx-3, lcsh:Chemistry, Cell Line, Tumor, hemic and lymphatic diseases, medicine, Tumor Microenvironment, Humans, Physical and Theoretical Chemistry, Molecular Biology, lcsh:QH301-705.5, Spectroscopy, chemistry.chemical_classification, reactive oxygen species, Reactive oxygen species, Glutathione Peroxidase, Chemistry, Organic Chemistry, Mesenchymal stem cell, Mesenchymal Stem Cells, General Medicine, leukemic cell, medicine.disease, microenvironment, Coculture Techniques, Computer Science Applications, Cell biology, Neoplasm Proteins, Gene Expression Regulation, Neoplastic, Metabolic pathway, Leukemia, Leukemia, Myeloid, Acute, medicine.anatomical_structure, Enzyme, lcsh:Biology (General), lcsh:QD1-999, mesenchymal stromal cell, Bone marrow, Oxidation-Reduction, Oxidative stress
Abstract

The bone marrow (BM) microenvironment plays a crucial role in the development and progression of leukemia (AML). Intracellular reactive oxygen species (ROS) are involved in the regulation of the biology of leukemia-initiating cells, where the antioxidant enzyme GPx-3 could be involved as a determinant of cellular self-renewal. Little is known however about the role of the microenvironment in the control of the oxidative metabolism of AML cells. In the present study, a coculture model of BM mesenchymal stromal cells (MSCs) and AML cells (KG1a cell-line and primary BM blasts) was used to explore this metabolic pathway. MSC-contact, rather than culture with MSC-conditioned medium, decreases ROS levels and inhibits the Nrf-2 pathway through overexpression of GPx3 in AML cells. The decrease of ROS levels also inactivates p38MAPK and reduces the proliferation of AML cells. Conversely, contact with AML cells modifies MSCs in that they display an increased oxidative stress and Nrf-2 activation, together with a concomitant lowered expression of GPx-3. Altogether, these experiments suggest that a reciprocal control of oxidative metabolism is initiated by direct cell&ndash, cell contact between MSCs and AML cells. GPx-3 expression appears to play a crucial role in this cross-talk and could be involved in the regulation of leukemogenesis.

Published
2020

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