Porphyromonas gingivalis triggers inflammatory responses in periodontal ligament cells by succinate-succinate dehydrogenase–HIF–1α axis

Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2020-01, Vol.522 (1), p.184-190
Main Authors: Su, Wenqi, Shi, Jiahong, Zhao, Yunhe, Yan, Fuhua, Lei, Lang, Li, Houxuan
Format: Article
Language:English
Subjects:
Bacteria
Metabolic reprogramming
Periodontal diseases
Succinate dehydrogenase
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Summary:Metabolic reprogramming from oxidative phosphorylation to glycolysis have been implicated in the pathogenesis of inflammatory diseases, such as pulmonary hypertension, rheumatoid arthritis and sepsis. Whether metabolic reprogramming participates in the progression of bacteriogenic periodontitis has never been reported. In the present study, we explored metabolic changes in periodontal ligament cells (PDLSCs) in response to Porphyromonas gingivalis. (P. gingivalis)-infected PDLSCs showed distinct metabolomics with metabolic reprogramming from oxidative phosphorylation to glycolysis. In addition, bacteria invasion triggered fundamental changes in glycolysis and tricarboxylate acid (TCA) cycle-related genes, such as the hexokinase (HK), isocitrate dehydrogenase (IDH) and succinate dehydrogenase (SDH). Moreover, P. gingivalis-infected PDLSCs showed accumulation of succinate, elevation in succinate dehydrogenase activity, pileup of reactive oxygen species and activation of hypoxia inducible factor-1α (HIF-1α) pathway. HIF-1α and succinate inhibitors, as well as SDH knockdown alleviated proinflammatory cytokine expression in P. gingivalis-infected PDLSCs. Therefore, targeting metabolic reprogramming by regulating the succinate-SDH–HIF–1α axis may facilitate host modulation therapy of chronic periodontitis. •P. gingivalis triggered metabolic reprogramming in periodontal ligament cells.•P. gingivalis infection upregulated IDH and SDH in the TCA cycle.•Succinate-SDH–HIF–1α axis drives inflammatory responses in PDLCs.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2019.11.074