ArticleExperimental & molecular medicine2010
Endoplasmic reticulum stress (ER-stress) by 2-deoxy-D-glucose (2DG) reduces cyclooxygenase-2 (COX-2) expression and N-glycosylation and induces a loss of COX-2 activity via a Src kinase-dependent pathway in rabbit articular chondrocytes.
Article in Experimental & molecular medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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30 citing papers in PubMed, 65 citations in OpenAlex.
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- Inhibition of Glycolysis Alleviates Chronic Unpredictable Mild Stress Induced Neuroinflammation and Depression-like Behavior.Brain sciences · 2024Article
- Novel insight on IRE1 in the regulation of chondrocyte dedifferentiation through ER stress independent pathway.Journal of physiology and biochemistry · 2024Article
- Glycolytic enzyme PKM2 regulates cell senescence but not inflammation in the process of osteoarthritis.Acta biochimica et biophysica Sinica · 2023Article
- Osteoarthritic chondrocytes undergo a glycolysis-related metabolic switch upon exposure to IL-1b or TNF.Cell communication and signaling : CCS · 2023Article
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- The combination of hydroxychloroquine and 2-deoxyglucose enhances apoptosis in breast cancer cells by blocking protective autophagy and sustaining endoplasmic reticulum stress.Cell death discovery · 2022Article
- PALMD regulates aortic valve calcification via altered glycolysis and NF-κB-mediated inflammation.The Journal of biological chemistry · 2022Article
- Glycolytic inhibitor 2-deoxy-d-glucose attenuates SARS-CoV-2 multiplication in host cells and weakens the infective potential of progeny virions.Life sciences · 2022Article
- Autophagy and organelle homeostasis in cancer.Developmental cell · 2021Review
- Impact of impaired glucose metabolism on responses to a psychophysical stressor: modulation by ketamine.Psychopharmacology · 2021Article
- Neutrophils Fuel Effective Immune Responses through Gluconeogenesis and Glycogenesis.Cell metabolism · 2021Article
- The role of antibody expression and their association with bladder cancer recurrence: a single-centre prospective clinical-pilot study in 35 patients.BMC urology · 2020Article
- The Human Cytomegalovirus UL38 protein drives mTOR-independent metabolic flux reprogramming by inhibiting TSC2.PLoS pathogens · 2019Article
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2 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
Endoplasmic reticulum (ER) stress regulates a wide range of cellular responses including apoptosis, proliferation, inflammation, and differentiation in mammalian cells. In this study, we observed the role of 2-deoxy-D-glucose (2DG) on inflammation of chondrocytes. 2DG is well known as an inducer of ER stress, via inhibition of glycolysis and glycosylation. Treatment of 2DG in chondrocytes considerably induced ER stress in a dose- and time-dependent manner, which was demonstrated by a reduction of glucose regulated protein of 94 kDa (grp94), an ER stress-inducible protein, as determined by a Western blot analysis. In addition, induction of ER stress by 2DG led to the expression of COX-2 protein with an apparent molecular mass of 66-70kDa as compared with the normally expressed 72-74 kDa protein. The suppression of ER stress with salubrinal (Salub), a selective inhibitor of eif2-alpha dephosphorylation, successfully prevented grp94 induction and efficiently recovered 2DG- modified COX-2 molecular mass and COX-2 activity might be associated with COX-2 N-glycosylation. Also, treatment of 2DG increased phosphorylation of Src in chondrocytes. The inhibition of the Src signaling pathway with PP2 (Src tyrosine kinase inhibitor) suppressed grp94 expression and restored COX-2 expression, N-glycosylation, and PGE2 production, as determined by a Western blot analysis and PGE2 assay. Taken together, our results indicate that the ER stress induced by 2DG results in a decrease of the transcription level, the molecular mass, and the activity of COX-2 in rabbit articular chondrocytes via a Src kinase-dependent pathway.
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