دورية أكاديمية
Lactate Protects Microglia and Neurons from Oxygen-Glucose Deprivation/Reoxygenation.
العنوان: | Lactate Protects Microglia and Neurons from Oxygen-Glucose Deprivation/Reoxygenation. |
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المؤلفون: | Tassinari ID; Graduate Program in Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, 90050-003, Brazil.; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YW, UK., Rodrigues FDS; Graduate Program in Biosciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil.; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YW, UK., Bertram C; School of Pharmacy and Biomedical Sciences, University of Central Lancashire, Preston, PR1 2HE, UK., Mendes-da-Cruz DA; Laboratory on Thymus Research, Oswaldo Cruz Institute, Oswaldo Cruz Foundation, Rio de Janeiro, 21040-360, Brazil.; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YW, UK., Guedes RP; Graduate Program in Biosciences, Federal University of Health Sciences of Porto Alegre (UFCSPA), Porto Alegre, 90050-170, Brazil., Paz AH; Graduate Program in Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, 90050-003, Brazil., Bambini-Junior V; Division of Biomedical and Life Sciences, Faculty of Health and Medicine, Lancaster University, Lancaster, LA1 4YW, UK., de Fraga LS; Graduate Program in Physiology, Institute of Basic Health Sciences (ICBS), Federal University of Rio Grande do Sul (UFRGS), Porto Alegre, 90050-003, Brazil. lucianof@ufrgs.br. |
المصدر: | Neurochemical research [Neurochem Res] 2024 Jul; Vol. 49 (7), pp. 1762-1781. Date of Electronic Publication: 2024 Mar 29. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Kluwer Academic/Plenum Publishers Country of Publication: United States NLM ID: 7613461 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1573-6903 (Electronic) Linking ISSN: 03643190 NLM ISO Abbreviation: Neurochem Res Subsets: MEDLINE |
أسماء مطبوعة: | Publication: 1999- : New York, NY : Kluwer Academic/Plenum Publishers Original Publication: New York, Plenum Press |
مواضيع طبية MeSH: | Microglia*/metabolism , Microglia*/drug effects , Glucose*/metabolism , Glucose*/deficiency , Neurons*/metabolism , Neurons*/drug effects , Oxygen*/metabolism , Lactic Acid*/metabolism , Cell Survival*/drug effects , Cell Survival*/physiology, Humans ; Animals ; Mice ; Neuroprotective Agents/pharmacology ; Cell Hypoxia/physiology ; Cell Hypoxia/drug effects ; Tumor Necrosis Factor-alpha/metabolism ; Receptors, G-Protein-Coupled/metabolism ; Cell Line, Tumor ; Cell Line ; Monocarboxylic Acid Transporters/metabolism |
مستخلص: | Lactate has received attention as a potential therapeutic intervention for brain diseases, particularly those including energy deficit, exacerbated inflammation, and disrupted redox status, such as cerebral ischemia. However, lactate roles in metabolic or signaling pathways in neural cells remain elusive in the hypoxic and ischemic contexts. Here, we tested the effects of lactate on the survival of a microglial (BV-2) and a neuronal (SH-SY5Y) cell lines during oxygen and glucose deprivation (OGD) or OGD followed by reoxygenation (OGD/R). Lactate signaling was studied by using 3,5-DHBA, an exogenous agonist of lactate receptor GPR81. Inhibition of lactate dehydrogenase (LDH) or monocarboxylate transporters (MCT), using oxamate or 4-CIN, respectively, was performed to evaluate the impact of lactate metabolization and transport on cell viability. The OGD lasted 6 h and the reoxygenation lasted 24 h following OGD (OGD/R). Cell viability, extracellular lactate concentrations, microglial intracellular pH and TNF-ɑ release, and neurite elongation were evaluated. Lactate or 3,5-DHBA treatment during OGD increased microglial survival during reoxygenation. Inhibition of lactate metabolism and transport impaired microglial and neuronal viability. OGD led to intracellular acidification in BV-2 cells, and reoxygenation increased the release of TNF-ɑ, which was reverted by lactate and 3,5-DHBA treatment. Our results suggest that lactate plays a dual role in OGD, acting as a metabolic and a signaling molecule in BV-2 and SH-SY5Y cells. Lactate metabolism and transport are vital for cell survival during OGD. Moreover, lactate treatment and GPR81 activation during OGD promote long-term adaptations that potentially protect cells against secondary cell death during reoxygenation. (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.) |
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فهرسة مساهمة: | Keywords: Lactate; Metabolism; Microglia; Neuron; Oxygen and glucose deprivation |
المشرفين على المادة: | IY9XDZ35W2 (Glucose) S88TT14065 (Oxygen) 33X04XA5AT (Lactic Acid) 0 (Neuroprotective Agents) 0 (Tumor Necrosis Factor-alpha) 0 (Receptors, G-Protein-Coupled) 0 (Monocarboxylic Acid Transporters) |
تواريخ الأحداث: | Date Created: 20240329 Date Completed: 20240601 Latest Revision: 20240601 |
رمز التحديث: | 20240602 |
DOI: | 10.1007/s11064-024-04135-7 |
PMID: | 38551797 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1573-6903 |
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DOI: | 10.1007/s11064-024-04135-7 |