Mycoplasma infection and hypoxia initiate succinate accumulation and release in the VM-M3 cancer cells

Flores, Roberto E.; Brown, Ashley K.; Taus, Luke J.; Khoury, Julianna; Glover, Frank; Kami, Kenjiro; Sarangarajan, Rangaprasad; Walshe, Tony E.; Narain, Niven R.; Kiebish, Michael A.; Shelton, Laura M.; Chinopoulos, Christos; Seyfried, Thomas N.

doi:10.1016/j.bbabio.2018.03.012

Cited by 20 publications

(16 citation statements)

References 49 publications

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“…Complete inhibition of OxPhos and glycolysis by oligomycin and 2-DG in CSCs and non-CSCs caused more substrate-level phosphorylation in uPAR+ CSCs. Under respiratory distress conditions, substrate-level phosphorylation provides the necessary GTP/ATP to CSCs and this is more efficient under hypoxic conditions ( 228 , 229 ). In vivo and ex vivo studies in OxPhos defective mtDNA mutated cybrid A6MT cells and wild type cells that have no mtDNA mutations, showed that Glutamine accelerates the proliferation of A6MT cell and its uptake was higher in mtDNA mutated cells than in wild type cells.…”

Section: Metabolism Of Glutamine In Cscsmentioning

confidence: 99%

Metabolic Adaptations in Cancer Stem Cells

et al. 2020

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Cancer stem cells (CSCs) are a small and elusive subpopulation of self-renewing cancer cells with remarkable ability to initiate, propagate, and spread the malignant disease. In addition, they exhibit increased resistance to anticancer therapies, thereby contributing to disease relapse. CSCs are reported to be present in many tumor types such as melanoma, sarcoma, mammary tumors, colon cancer and other solid tumors. These cells from different tumors show unique energetic and metabolic pathways. For example, CSCs from one type of tumor may predominantly use aerobic glycolysis, while from another tumor type may utilize oxidative phosphorylation. Most commonly these cells use fatty acid oxidation and ketone bodies as the main source of energy production. CSCs have a remarkable ability to reprogram their metabolism in order to survive under adverse conditions such as hypoxia, acidosis, and starvation. There is increasing interest to identify molecular targets that can be utilized to kill CSCs and to control their growth. In this review, we discuss how an understanding of the unique metabolism of CSCs from different tumors can offer promising strategies for targeting CSCs and hence to prevent disease relapse and to treat the metastatic disease.

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Section: Metabolism Of Glutamine In Cscsmentioning

confidence: 99%

Metabolic Adaptations in Cancer Stem Cells

et al. 2020

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“…Dysbiosis is observed in lungs of patients of COPD, in that the composition of lungs microbiota is less diverse than the one observed in healthy persons, and has a tendency to be restricted to phyla comprising potentially pathogenic microorganism, including M. pneumoniae [24,27,28], also associated with acute exacerbation [29,30]. Some of the mechanisms by which M. pneumoniae could enhance the negative effects of tobacco products in COPD patients is by increasing oxidative stress [31], inflammation status and hypoxia-related factors, such as HIF-1α [32]. Quitting smoking in combination with anti-muscarinic bronchodilators resulted in an improvement of lung function and respiratory symptoms in mild COPD patients and it could be interesting to determine whether this would also result in a reduction in dysbiosis and the presence of M. pneumoniae [24].…”

Section: Mycoplasma and Copdmentioning

confidence: 99%

Role of Mycoplasma Chaperone DnaK in Cellular Transformation

Benedetti

Cocchi

Latinovic

et al. 2020

IJMS

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Studies of the human microbiome have elucidated an array of complex interactions between prokaryotes and their hosts. However, precise bacterial pathogen–cancer relationships remain largely elusive, although several bacteria, particularly those establishing persistent intra-cellular infections, like mycoplasmas, can alter host cell cycles, affect apoptotic pathways, and stimulate the production of inflammatory substances linked to DNA damage, thus potentially promoting abnormal cell growth and transformation. Consistent with this idea, in vivo experiments in several chemically induced or genetically deficient mouse models showed that germ-free conditions reduce colonic tumor formation. We demonstrate that mycoplasma DnaK, a chaperone protein belonging to the Heath shock protein (Hsp)-70 family, binds Poly-(ADP-ribose) Polymerase (PARP)-1, a protein that plays a critical role in the pathways involved in recognition of DNA damage and repair, and reduces its catalytic activity. It also binds USP10, a key p53 regulator, reducing p53 stability and anti-cancer functions. Finally, we showed that bystander, uninfected cells take up exogenous DnaK—suggesting a possible paracrine function in promoting cellular transformation, over and above direct mycoplasma infection. We propose that mycoplasmas, and perhaps certain other bacteria with closely related DnaK, may have oncogenic activity, mediated through the inhibition of DNA repair and p53 functions, and may be involved in the initiation of some cancers but not necessarily involved nor necessarily even be present in later stages.

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“…Succinate plays important role in the inflammation process (Mills & O'Neill, ; Tannahill et al, ). Calcium‐dependent NO and PGE2 production were observed following stimulation of SUCNR1 with succinate (Flores et al, ; Tannahill et al, ). Succinate acts in synergy with the TLR3 ligand poly (I:C) and the TLR7 ligand imiquimod, thereby increasing the TNF‐ α production and expression (Tannahill et al, ).…”

Section: Discussionmentioning

confidence: 99%

Urinary metabolomics analysis reveals the effect of volatile oil from Angelica sinensis on LPS‐induced inflammation rats

Hua

Zhang

et al. 2018

Biomedical Chromatography

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Lipopolysaccharide (LPS)-induced inflammation occurs commonly and volatile oil fromAngelica sinensis (VOAS) can be used as an anti-inflammatory agent. The molecular mechanisms that allow the anti-inflammatory factors to be expressed are still unknown. In this paper, we applied gas chromatography-mass spectrometry (GC-MS) and high-performance liquid chromatography-time-of-flight mass spectrometry (LC-Q/TOF-MS) based on a metabolomics platform coupled with a network approach to analyze urine samples in three groups of rats: one with LPS-induced inflammation (MI); one with intervention with VOAS; and normal controls (NC). Our study found definite metabolic footprints of inflammation and showed that all three groups of rats, MI, intervention with VOAS and NC have distinct metabolic profiles in urine. The concentrations of 48 metabolites differed significantly among the three groups. The metabolites in urine were screened by the GC-MS and LC-Q/TOF-MS methods.The significantly changed metabolites (p < 0.05, variable importance in projection > 1.5) between MI, NC and VOAS were included in the metabolic networks.Finally, hub metabolites were screened, including glycine, arachidonic acid, L-glutamate, pyruvate and succinate, which have high values of degree (k). the Results suggest that disorders of glycine, arachidonic acid, L-glutamate, pyruvate and succinate metabolism might play an important part in the predisposition and development of LPS-induced inflammation. By applying metabolomics with network methods, the mechanisms of diseases are clearly elucidated.

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Mycoplasma infection and hypoxia initiate succinate accumulation and release in the VM-M3 cancer cells

Cited by 20 publications

References 49 publications

Metabolic Adaptations in Cancer Stem Cells

Metabolic Adaptations in Cancer Stem Cells

Role of Mycoplasma Chaperone DnaK in Cellular Transformation

Urinary metabolomics analysis reveals the effect of volatile oil from Angelica sinensis on LPS‐induced inflammation rats

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