Metabolic shift in the production of corrinoid compounds by Lactobacillus coryniformis in the absence of purines

Metabolic reprogramming promotes glioblastoma cell migration and invasion. Integrin αvβ3 is one of the major integrin family members in glioblastoma multiforme cell surface mediating interactions with extracellular matrix proteins that are important for glioblastoma progression. The role of αvβ3 integrin in regulating metabolic reprogramming and its mechanism of action have not been determined in glioblastoma cells. Integrin αvβ3 engagement with osteopontin promotes glucose uptake and aerobic glycolysis, while inhibiting mitochondrial oxidative phosphorylation. Blocking or downregulation of integrin αvβ3 inhibits glucose uptake and aerobic glycolysis and promotes mitochondrial oxidative phosphorylation, resulting in decreased migration and growth in glioblastoma cells. Pharmacological inhibition of focal adhesion kinase (FAK) or downregulation of protein arginine methyltransferase 5 (PRMT5) blocks metabolic shift toward glycolysis and inhibits glioblastoma cell migration and invasion. These results support that integrin αvβ3 and osteopontin engagement plays an important role in promoting the metabolic shift toward glycolysis and inhibiting mitochondria oxidative phosphorylation in glioblastoma cells. The metabolic shift in cell energy metabolism is coupled to changes in migration, invasion, and growth, which are mediated by downstream FAK and PRMT5 in glioblastoma cells.

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Carbon Monoxide-Neuroglobin Axis Targeting Metabolism Against Neuroinflammation

10.21203/rs.3.rs-852619/v1 ◽

2021 ◽

Author(s):

Daniela Dias-Pedroso ◽

José S. Ramalho ◽

Vilma A. Sardão ◽

John G. Jones ◽

Carlos C. Romão ◽

...

Keyword(s):

Nitric Oxide ◽

Carbon Monoxide ◽

Oxygen Consumption ◽

Inflammatory Response ◽

Microglial Cell ◽

Cell Metabolism ◽

Competent Cell ◽

Metabolic Shift ◽

Anti Inflammatory ◽

Inflammatory Effect

Abstract Microglia are the immune competent cell of the central nervous system (CNS), promoting brain homeostasis and regulating inflammatory response against infection and injury. Chronic or exacerbated neuroinflammation is a cause of damage in several brain pathologies. Endogenous carbon monoxide (CO), produced from the degradation of heme, is described as anti-apoptotic and anti-inflammatory in several contexts, including in the CNS. Neuroglobin (Ngb) is a haemoglobin-homologous protein, which upregulation triggers antioxidant defence and prevents neuronal apoptosis. Thus, we hypothesized a crosstalk between CO and Ngb, in particular, that the anti-neuroinflammatory role of CO in microglia depends on Ngb. A novel CO-releasing molecule (ALF826) based on molybdenum was used for delivering CO in microglial culture.BV-2 mouse microglial cell line was challenged with lipopolysaccharide (LPS) for triggering inflammation, and after 6h ALF826 was added. CO exposure limited inflammation by decreasing inducible nitric oxide synthase (iNOS) expression and the production of nitric oxide (NO) and tumour necrosis factor-a (TNF-a), and by increasing interleukine-10 (IL-10) release. CO-induced Ngb upregulation correlated in time with CO’s anti-inflammatory effect. Moreover, knocking down Ngb reversed the anti-inflammatory effect of CO, suggesting that dependents on Ngb expression. CO-induced Ngb upregulation was independent on ROS signalling, but partially dependent on the transcriptional factor SP1. Finally, microglial cell metabolism is also involved in the inflammatory response. In fact, LPS treatment decreased oxygen consumption in microglia, indicating a switch to glycolysis, which is associated with a proinflammatory. While CO treatment increased oxygen consumption, reverting LPS effect and indicating a metabolic shift into a more oxidative metabolism. Moreover, in the absence of Ngb this phenotype was no longer observed, indicating Ngb is needed for CO’s modulation of microglial metabolism. Finally, the metabolic shift induced by CO did not depend on alteration of mitochondrial population. In conclusion, neuroglobin emerges for the first time as a key player for CO signalling against exacerbated neuroinflammation in microglia.

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Characters of Lactobacillus coryniformis, isolated from an Iraqi cheese

Zentralblatt für Bakteriologie Parasitenkunde Infektionskrankheiten und Hygiene Zweite Naturwissenschaftliche Abteilung Mikrobiologie der Landwirtschaft der Technologie und des Umweltschutzes ◽

10.1016/s0323-6056(80)80024-3 ◽

1980 ◽

Vol 135 (3) ◽

pp. 205-211 ◽

Cited By ~ 2

Author(s):

F.Z. Hegazi ◽

I.G. Abo-Elnaga

Keyword(s):

Lactobacillus Coryniformis

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miR-206 regulates a metabolic switch in nasopharyngeal carcinoma by suppressing HK2 expression

10.21203/rs.3.rs-43672/v1 ◽

2020 ◽

Author(s):

Chunying Luo ◽

Min Liu ◽

Jianwei Zhang ◽

Guoqiang Su ◽

Zhonghua Wei

Keyword(s):

Nasopharyngeal Carcinoma ◽

Warburg Effect ◽

Carcinoma Cells ◽

Luciferase Reporter ◽

Metabolic Shift ◽

Invasion And Metastasis ◽

Metabolic Switch ◽

And Function ◽

The Relationship

Abstract Background: Many studies have shown that microRNAs play key functions in nasopharyngeal carcinoma proliferation, invasion and metastasis. However, whether the dysregulated level of miRNAs contributes to the metabolic shift in nasopharyngeal carcinoma is not completely understood.Objectives: This study was conducted to explore the expression and function of miR-206 in nasopharyngeal carcinoma.Methods: miR-206 expression level was examined by real-time PCR. miR-206 inhibitor, mimics, and scrambled control were transiently transfected into nasopharyngeal carcinoma cells and their effects on colony formation, glucose uptake, and lactate secretion were observed in vitro. Moreover, the relationship between the levels of miR-206 and HK2 was examined by luciferase reporter and assay western blot.Results: In our study, we reported downregulation of miR-206 expression leads to metabolic change in nasopharyngeal carcinoma cells. miR-206 controls this function by enhancing HK2 expression. The enhancement of aerobic metabolism activity induced by miR-206 leads to the rapid proliferation of nasopharyngeal carcinoma cells.Conclusions: Our data demonstrated that miR-206 was involved in the regulation of Warburg effect in nasopharyngeal carcinoma by suppressing HK2 expression.

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WRN modulates translation by influencing mRNA export from the nucleus through its interaction with the export receptor NXF1 in HeLa cancer cell

10.21203/rs.3.rs-33612/v2 ◽

2020 ◽

Author(s):

Juan Manuel Iglesias-Pedraz ◽

Diego Matia Fossatti Jara ◽

Valeria Del Carmen Valle-Riestra Felice ◽

Sergio Rafael Cruz Visalaya ◽

Jose Antonio Ayala Felix ◽

...

Keyword(s):

Oxidative Stress ◽

Protein Synthesis ◽

Cancer Cells ◽

Nuclear Export ◽

Werner Syndrome ◽

Mrna Export ◽

Premature Aging ◽

Metabolic Shift ◽

Loss Of Function ◽

Global Protein Synthesis

Abstract Background The Werner syndrome protein (WRN) belongs to the RecQ family of helicases and its loss of function results in the premature aging disease Werner syndrome (WS). We previously demonstrated that an early cellular change induced by WRN depletion is a posttranscriptional decrease in the levels of enzymes involved in metabolic pathways that control macromolecular synthesis and protect from oxidative stress. This metabolic shift is tolerated by normal cells but causes mitochondria dysfunction and acute oxidative stress in rapidly growing cancer cells, thereby suppressing their proliferation.Results To identify the mechanism underlying this metabolic shift, we examined global protein synthesis and mRNA nucleocytoplasmic distribution after WRN knockdown. We determined that WRN depletion in HeLa cells attenuates global protein synthesis without affecting the level of key components of the mRNA export machinery. We further observed that WRN depletion affects the nuclear export of mRNAs and demonstrated that WRN directly interacts with mRNA and the mRNA export receptor Nuclear Export Factor 1 (NXF1).Conclusions Our findings suggest that WRN influences the export of mRNAs from the nucleus through its interaction with the NXF1 export receptor thereby affecting cellular proteostasis. In summary, we identified a new partner and a novel function of WRN, which is especially important for the proliferation of cancer cells.

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