Glioma Cells Are Resistant To Inflammation-Induced Alterations Of Mitochondrial Dynamics

INTERNATIONAL JOURNAL OF ONCOLOGY(2020)

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摘要
Accumulating evidence suggests that inflammation is present in solid tumors. However, it is poorly understood whether inflammation exists in glioma and how it affects the metabolic signature of glioma. By analyzing immunohistochemical data and gene expression data downloaded from bioinformatic datasets, the present study revealed an accumulation of inflammatory cells in glioma, activation of microglia, upregulation of proinflammatory factors (including IL-6, IL-8, hypoxia-inducible factor-1 alpha, STAT3, NF-kappa B1 and NF-kappa B2), destruction of mitochondrial structure and altered expression levels of electron transfer chain complexes and metabolic enzymes. By monitoring glioma cells following proinflammatory stimulation, the current study observed a remodeling of their mitochondrial network via mitochondrial fission. More than half of the mitochondria presented ring-shaped or spherical morphologies. Transmission electron microscopic analyses revealed mitochondrial swelling with partial or total cristolysis. Furthermore, proinflammatory stimuli resulted in increased generation of reactive oxygen species, decreased mitochondrial membrane potential and reprogrammed metabolism. The defective mitochondria were not eliminated via mitophagy. However, cell viability was not affected, and apoptosis was decreased in glioma cells after proinflammatory stimuli. Overall, the present findings suggested that inflammation may be present in glioma and that glioma cells may be resistant to inflammation-induced mitochondrial dysfunction.
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关键词
apoptosis, glioma, inflammation, metabolic reprogramming, mitochondrial network, mitophagy
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