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Inflammatory response of microglial BV‐2 cells includes a glycolytic shift and is modulated by mitochondrial glucose‐regulated protein 75/mortalin
Author(s) -
Voloboueva Ludmila A.,
Emery John F.,
Sun Xiaoyun,
Giffard Rona G.
Publication year - 2013
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2013.01.067
Subject(s) - proinflammatory cytokine , mitochondrion , microbiology and biotechnology , glycolysis , inflammation , oxidative phosphorylation , chemistry , mitochondrial ros , cytokine , downregulation and upregulation , biochemistry , biology , metabolism , immunology , gene
Recent studies suggest a link between mitochondria and proinflammatory cytokine generation. We previously demonstrated that overexpression of mitochondrial chaperone glucose‐regulated protein75 (Grp75/mortalin) protects mitochondria. In this study we investigated the modulation of the lipopolisaccharide (LPS)‐induced inflammatory response of microglial BV‐2 cells by Grp75. We demonstrate that LPS‐induced activation promotes significant metabolic changes suppressing mitochondrial function and increasing glycolysis. Overexpression of Grp75 attenuates the LPS‐induced oxidative and metabolic responses, and suppresses proinflammatory activation, which depends on both NF‐κB activation and lactate. Thus overexpression of Grp75 provides a novel strategy to modulate proinflammatory cytokine production of relevance to inflammation‐associated pathologies.