Academic Journal
The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress
| العنوان: | The Chemically-Modified Tetracycline COL-3 and Its Parent Compound Doxycycline Prevent Microglial Inflammatory Responses by Reducing Glucose-Mediated Oxidative Stress |
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| المؤلفون: | Nilson Carlos Ferreira Junior, Maurício dos Santos Pereira, Nour Francis, Paola Ramirez, Paula Martorell, Florencia González-Lizarraga, Bruno Figadère, Rosana Chehin, Elaine Del Bel, Rita Raisman-Vozari, Patrick Pierre Michel |
| المصدر: | Cells, Vol 10, Iss 8, p 2163 (2021) |
| بيانات النشر: | MDPI AG, 2021. |
| سنة النشر: | 2021 |
| المجموعة: | LCC:Cytology |
| مصطلحات موضوعية: | COL-3, glucose metabolism, microglia, NADPH oxidase, neuroinflammation, oxidative stress, Cytology, QH573-671 |
| الوصف: | 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. |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 2073-4409 |
| Relation: | https://www.mdpi.com/2073-4409/10/8/2163; https://doaj.org/toc/2073-4409 |
| DOI: | 10.3390/cells10082163 |
| URL الوصول: | https://doaj.org/article/169e7458233e4103830aad8ef1822ab6 |
| رقم الانضمام: | edsdoj.169e7458233e4103830aad8ef1822ab6 |
| قاعدة البيانات: | Directory of Open Access Journals |
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