Overcoming the Warburg Effect: Is it the key to survival in sepsis?

Bar‐Or, David; Carrick, Matthew M.; Tanner, Allen; Lieser, Mark; Rael, Leonard T.; Brody, Edward N.

doi:10.1016/j.jcrc.2017.09.012

Cited by 54 publications

(43 citation statements)

References 51 publications

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“…The iTRAQ-based quantitative proteomics identified 205 DEPs between ovarian cancer and control tissues [13], which revealed the upregulation of the key enzyme PKM2 in glycolysis pathway I in ovarian cancers. It was coincided with the Otto Warburg effect proposed in 1956 [30].…”

Section: The Changes Of Key Proteins In the Energy Metabolism Signalimentioning

confidence: 99%

“…Cancer cells and stroma cells (especially CAFs) have metabolic symbiosis, so cancer cells induce oxidative stress of CAFs by secreting ROS to enhance aerobic glycolysis of CAFs. In turn, CAFs produced lots of nourishment to be 'eaten' up by cancer cells for producing ATP through Krebs cycle and oxidative phosphorylation [13].…”

Section: Potential Therapeutic Targets In Metabolic Symbiosismentioning

confidence: 99%

“…Consequently, CAFs secrete plenty of energy-rich fuels to TME, including ketone bodies, lactate, pyruvate, and fatty acids. In turn, the nourishment 'feed' mitochondrial oxidative phosphorylation and ATP supplements [13]. In this process, mono-carboxylate transporters (MCTs) were highly expressed in both cancer cells and CAFs to be involved in some regulations.…”

Section: Introductionmentioning

confidence: 99%

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Energy Metabolism Heterogeneity-Based Molecular Biomarkers for Ovarian Cancer

Li¹,

Zhan²,

Zhan³

2019

Molecular Medicine

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Energy metabolism heterogeneity is a hallmark in ovarian cancer; namely, the Warburg and reverse Warburg effects coexist in ovarian cancer. Exploration of energy metabolism heterogeneity benefits the discovery of the effective biomarkers for ovarian cancers. The integrative analysis of transcriptomics (20,115 genes in 419 ovarian cancer samples), proteomics (205 differentially expressed proteins), and mitochondrial proteomics (1198 mitochondrial differentially expressed proteins) revealed (i) the upregulations of rate-limiting enzymes PKM2 in glycolysis, IDH2 in Krebs cycle, and UQCRH in oxidative phosphorylation (OXPHOS) pathways, (ii) the upregulation of PDHB that converts pyruvate from glycolysis into acetyl-CoA in Krebs cycle, and (iii) that miRNA (hsa-miR-186-5p) and RNA-binding protein (EIF4AIII) had target sites in those key proteins in energy metabolism pathways. Furthermore, lncRNA SNHG3 interacted with miRNA (hsa-miR-186-5p) and RNA-binding protein (EIF4AIII). Those results were confirmed in the ovarian cancer cell model and tissues. It clearly concluded that lncRNA SNHG3 regulates energy metabolism through miRNA (hsa-miR-186-5p) and RNA-binding protein (EIF4AIII) to regulate the key proteins in the energy metabolism pathways. SNHG3 inhibitor might interfere with the energy metabolism to treat ovarian cancers. These findings provide more accurate understanding of molecular mechanisms of ovarian cancers and discovery of effective energy-metabolism-heterogeneity therapeutic drug for ovarian cancers. Highlights • Mitochondrial proteomics revealed the energy metabolism heterogeneity in ovarian cancers. • LncRNA SNHG3 was related to ovarian cancer survival and energy metabolism with ovarian cancer TCGA analysis. • SNHG3 was related to energy metabolism by regulating miRNAs and EIF4AIII based on GSEA and Starbase analyses. • MiRNAs and EIF4AIII regulate the glycolysis, Krebs cycle, and OXPHOS pathways by targeting PKM, PDHB, IDH2, and UQCRH.

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Section: The Changes Of Key Proteins In the Energy Metabolism Signalimentioning

confidence: 99%

Section: Potential Therapeutic Targets In Metabolic Symbiosismentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Energy Metabolism Heterogeneity-Based Molecular Biomarkers for Ovarian Cancer

Li¹,

Zhan²,

Zhan³

2019

Molecular Medicine

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“…Some viruses are able to drastically alter glucose metabolism in infected cells by diverting it from the tricarboxylic acid cycle (TCA) and enhancing its use for the production of fatty acids and lipids, which are needed for the synthesis of the membranes required for virion envelopes, ensuring in this way greater success of the virus infection [27,28,29]. In some processes of inflammation and sepsis produced by LPS, glucose metabolism is altered [30], and a metabolic switch from oxidative phosphorylation to aerobic glycolysis has been also observed in some cases [31].…”

Section: Accepted Manuscriptmentioning

confidence: 99%

“…In mammals, the Warburg effect appears to participate in the metabolic regulation of proinflammatory cytokines [64] and has been described to play a role in inflammation and sepsis [31]. Bacterial sepsis affects the ability of target tissues to utilize glucose via glycolysis and alternative fuel sources, such as ketone bodies and…”

Section: Accepted Manuscriptmentioning

confidence: 99%

β-glucan administration induces metabolic changes and differential survival rates after bacterial or viral infection in turbot (Scophthalmus maximus)

Librán-Pérez

Costa

Figueras

et al. 2018

Fish & Shellfish Immunology

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The innate immune response is able to ward off pathogens and remember previous infections using different mechanisms; this kind of immune reaction has been called "trained immunity". Changes in cellular metabolism (aerobic glycolysis) have been observed during training with some immunostimulants like β-glucans or during viral and bacterial infections. We hypothesize that β-glucans can induce metabolic changes used by the host to fight pathogens. Accordingly, we evaluated changes in metabolic parameters in turbot that could affect their survival after a previous intraperitoneal treatment with β-glucans and subsequent administration of Viral Hemorrhagic Septicemia Virus (VHSV) or bacteria (Aeromonas salmonicida subsp. salmonicida). The results obtained support that β-glucans, VHSV and A. salmonicida induce changes in lactate, glucose and ATP levels in plasma, head kidney and liver and in the mRNA expression of enzymes related to glucose and fatty acid metabolism in head kidney. Additionally, the metabolic changes induced by β-glucans are beneficial for VHSV replication, but they are harmful to A. salmonicida, resulting in reduced mortality. β-glucans appear to have great therapeutic potential and can induce trained immunity against bacterial disease but not against viral disease, which seems to take advantage of β-glucan metabolic alterations.

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Oxaloacetate induces apoptosis in HepG2 cells via inhibition of glycolysis

Kuang

Han

et al. 2018

Cancer Medicine

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Most cancer cells perform glycolysis despite having sufficient oxygen. The specific metabolic pathways of cancer cells have become the focus of cancer treatment. Recently, accumulating evidence indicates oxidative phosphorylation (OXPHOS) and glycolysis can be regulated with each other. Thus, we suggest that the glycolysis of cancer cells is inhibited by restoring or improving OXPHOS in cancer cells. In our study, we found that oxaloacetate (OA) induced apoptosis in HepG2 cells in vivo and in vitro. Meanwhile, we found that OA induced a decrease in the energy metabolism of HepG2 cells. Further results showed that the expression and activity of glycolytic enzymes were decreased with OA treatment. Conversely, the expression and activity of enzymes involved in the TCA cycle and OXPHOS were increased with OA treatment. The results indicate that OA can inhibit glycolysis through enhancement of OXPHOS. In addition, OA‐mediated suppression of HIF1α, p‐Akt, and c‐myc led to a decrease in glycolysis level. Therefore, OA has the potential to be a novel anticancer drug.

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Overcoming the Warburg Effect: Is it the key to survival in sepsis?

Cited by 54 publications

References 51 publications

Energy Metabolism Heterogeneity-Based Molecular Biomarkers for Ovarian Cancer

Energy Metabolism Heterogeneity-Based Molecular Biomarkers for Ovarian Cancer

β-glucan administration induces metabolic changes and differential survival rates after bacterial or viral infection in turbot (Scophthalmus maximus)

Oxaloacetate induces apoptosis in HepG2 cells via inhibition of glycolysis

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