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dc.contributor.author
Ferreira Junior, Nilson Carlos
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Dos Santos Pereira, Maurício
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Francis, Nour
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Ramirez, Paola
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Martorell, Paula
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González Lizarraga, Maria Florencia
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Figadère, Bruno
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Chehin, Rosana Nieves
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del Bel Belluz Guimaraes, Elaine
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Raisman Vozari, Rita
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Michel, Patrick Pierre
dc.date.available
2022-10-05T13:56:33Z
dc.date.issued
2021-08-22
dc.identifier.citation
Ferreira Junior, Nilson Carlos; Dos Santos Pereira, Maurício; Francis, Nour; Ramirez, Paola; Martorell, Paula; et al.; The chemically-modified tetracycline COL-3 and its parent compound doxycycline prevent microglial inflammatory responses by reducing glucose-mediated oxidative stress; MDPI; Cells; 10; 8; 22-8-2021; 1-16
dc.identifier.issn
2073-4409
dc.identifier.uri
http://hdl.handle.net/11336/171941
dc.description.abstract
We used mouse microglial cells in culture activated by lipopolysaccharide (LPS) or α-synuclein amyloid aggregates (αSa) to study the anti-inflammatory effects of COL-3, a tetracycline derivative without antimicrobial activity. Under LPS or αSa stimulation, COL-3 (10, 20 µM) efficiently repressed the induction of the microglial activation marker protein Iba-1 and the stimulated-release of the pro-inflammatory cytokine TNF-α. COL-3′s inhibitory effects on TNF-α were reproduced by the tetracycline antibiotic doxycycline (DOX; 50 µM), the glucocorticoid dexamethasone, and apocynin (APO), an inhibitor of the superoxide-producing enzyme NADPH oxidase. This last observation suggested that COL-3 and DOX might also operate themselves by restraining oxidative stress-mediated signaling events. Quantitative measurement of intracellular reactive oxygen species (ROS) levels revealed that COL-3 and DOX were indeed as effective as APO in reducing oxidative stress and TNF-α release in activated microglia. ROS inhibition with COL-3 or DOX occurred together with a reduction of microglial glucose accumulation and NADPH synthesis. This suggested that COL-3 and DOX might reduce microglial oxidative burst activity by limiting the glucose-dependent synthesis of NADPH, the requisite substrate for NADPH oxidase. Coherent with this possibility, the glycolysis inhibitor 2-deoxy-D-glucose reproduced the immunosuppressive action of COL-3 and DOX in activated microglia. Overall, we propose that COL-3 and its parent compound DOX exert anti-inflammatory effects in microglial cells by inhibiting glucose-dependent ROS production. These effects might be strengthened by the intrinsic antioxidant properties of DOX and COL-3 in a self-reinforcing manner.
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application/pdf
dc.language.iso
eng
dc.publisher
MDPI
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
COL-3
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GLUCOSE METABOLISM
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MICROGLIA
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NADPH OXIDASE
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NEUROINFLAMMATION
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OXIDATIVE STRESS
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TETRACYCLINES
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Otras Medicina Básica
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Medicina Básica
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CIENCIAS MÉDICAS Y DE LA SALUD
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dc.title
The chemically-modified tetracycline COL-3 and its parent compound doxycycline prevent microglial inflammatory responses by reducing glucose-mediated oxidative stress
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2022-09-29T10:59:18Z
dc.journal.volume
10
dc.journal.number
8
dc.journal.pagination
1-16
dc.journal.pais
Suiza
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dc.journal.ciudad
Basilea
dc.description.fil
Fil: Ferreira Junior, Nilson Carlos. Universidade de Sao Paulo; Brasil. Sorbonne University; Francia
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Fil: Dos Santos Pereira, Maurício. Universidade de Sao Paulo; Brasil. Sorbonne University; Francia
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Fil: Francis, Nour. Sorbonne University; Francia
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Fil: Ramirez, Paola. Sorbonne University; Francia
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Fil: Martorell, Paula. Sorbonne University; Francia
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Fil: González Lizarraga, Maria Florencia. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; Argentina
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Fil: Figadère, Bruno. Center for Interdisciplinary Research on Applied Neurosciences; Brasil
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Fil: Chehin, Rosana Nieves. Universidad Nacional de Tucumán. Instituto de Investigaciones En Medicina Molecular y Celular Aplicada del Bicentenario. - Gobierno de la Provincia de Tucumán. Ministerio de Salud. Sistema Provincial de Salud. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario. - Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet Noa Sur. Instituto de Investigaciones en Medicina Molecular y Celular Aplicada del Bicentenario; Argentina
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Fil: del Bel Belluz Guimaraes, Elaine. Universidade de Sao Paulo; Brasil
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Fil: Raisman Vozari, Rita. Sorbonne University; Francia
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Fil: Michel, Patrick Pierre. Sorbonne University; Francia
dc.journal.title
Cells
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info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.3390/cells10082163
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info:eu-repo/semantics/altIdentifier/url/https://www.mdpi.com/2073-4409/10/8/2163
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