Thermodynamics in cancers: opposing interactions between PPAR gamma and the canonical WNT/beta‐catenin pathway

Lecarpentier, Yves; Claes, Victor; Vallée, Alexandre; Hébert, Jean-Louis

doi:10.1186/s40169-017-0144-7

Cited by 65 publications

(59 citation statements)

References 174 publications

(185 reference statements)

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“…Several studies have shown that aerobic glycolysis is induced by overactivation of the WNT/β-catenin pathway through a direct activation of PDK1 and MCT-1 [ 31 , 35 , 96 , 97 ]. β-catenin activation induces the expression of PI3K/Akt signaling [ 56 , 57 ].…”

Section: Introductionmentioning

confidence: 99%

Warburg effect hypothesis in autism Spectrum disorders

Vallée

2018

Mol Brain

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Autism spectrum disorder (ASD) is a neurodevelopmental disease which is characterized by a deficit in social interactions and communication with repetitive and restrictive behavior. In altered cells, metabolic enzymes are modified by the dysregulation of the canonical WNT/β-catenin pathway. In ASD, the canonical WNT/β-catenin pathway is upregulated. We focus this review on the hypothesis of Warburg effect stimulated by the overexpression of the canonical WNT/β-catenin pathway in ASD. Upregulation of WNT/β-catenin pathway induces aerobic glycolysis, named Warburg effect, through activation of glucose transporter (Glut), pyruvate kinase M2 (PKM2), pyruvate dehydrogenase kinase 1(PDK1), monocarboxylate lactate transporter 1 (MCT-1), lactate dehydrogenase kinase-A (LDH-A) and inactivation of pyruvate dehydrogenase complex (PDH). The aerobic glycolysis consists to a supply of a large part of glucose into lactate regardless of oxygen. Aerobic glycolysis is less efficient in terms of ATP production than oxidative phosphorylation because of the shunt of the TCA cycle. Dysregulation of energetic metabolism might promote cell deregulation and progression of ASD. Warburg effect regulation could be an attractive target for developing therapeutic interventions in ASD.

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Section: Introductionmentioning

confidence: 99%

Warburg effect hypothesis in autism Spectrum disorders

Vallée

2018

Mol Brain

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“…Pyruvic acid could enter the TCA cycle and be completely oxidized in aerobic conditions, or could become lactic acid under anaerobic conditions [46,47]. HIF-1α could prevent the production of ATP and thus regulate the glycolysis of mouse granulosa cells [48].…”

Section: Discussionmentioning

confidence: 99%

Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and enhances glycolysis in macrophages

Chen

Zhang

et al. 2020

Preprint

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Background: Salmonella enterica serovar Typhimurium ( S. Typhimurium) is an important infectious disease pathogen that can survive and replicate in macrophages. Glycolysis is essential for immune responses against S. Typhimurium infection in macrophages, and is also associated with apoptosis. S. Typhimurium secreted effector K3 (SseK3) was recently identified as a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis in cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in S. Typhimurium-infected macrophages. Results: Macrophages were infected with S. Typhimurium SL1344 wild-type (WT), Δ sseK3 mutant or sseK3 -complemented strain, and the effects of sseK3 on apoptosis and glycolysis were determined. The adherence and invasion in the Δ sseK3 mutant group were similar to that in the WT and sseK3 -complemented groups, indicating that SseK3 was not essential for the adherence and invasion of S. Typhimurium in macrophages. However, the percentage of apoptosis in the Δ sseK3 mutant group was much lower than that in the WT and sseK3 -complemented groups. Caspase-3, caspase-8, and caspase-9 enzyme activity in the Δ sseK3 mutant group were significantly lower than in the WT group and sseK3 -complemented groups, indicating that sseK3 could improve the caspase-3, caspase-8, and caspase-9 enzyme activity. We also found that there were no significant differences in pyruvic acid levels between the three groups, but the lactic acid level in the Δ sseK3 mutant group was much lower than that in the WT and sseK3 -complemented groups. The ATP levels in the Δ sseK3 mutant group were remarkably higher than those in the WT and sseK3 -complemented groups. These indicated that the sseK3 enhanced the level of glycolysis in macrophages infected by S. Typhimurium. Conclusions: S. Typhimurium sseK3 is likely involved in promoting macrophage apoptosis and modulating glycolysis in macrophages. Our results could improve our understanding of the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3 .

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“…There have various metabolic pathway to produce pyruvic acid [43]. Pyruvic acid could enter the TCA cycle to be completely oxidized in aerobic condition, whereas it could become lactic acid under anaerobic oxygen condition [44,45]. HIF-1α could prohibit the production of ATP and thus regulate the glycolysis of mouse granulosa cells [46].…”

Section: Discussionmentioning

confidence: 99%

The Salmonella enterica serovar Typhimurium sseK3 induce cell apoptosis and enhance glycolysis in macrophages

Chen

Zhang³

et al. 2020

Preprint

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Background: Salmonella enterica serovar Typhimurium (S. Typhimurium) is an important infectious disease pathogen. Recently, there are increasing researches about the relationship between apoptosis and glycolysis of cells. Previous studies have identified that S. Typhimurium secreted effector K3 (SseK3) is a novel translated and secreted protein. However, there is no study about the role of sseK3 in the relationship between apoptosis and glycolysis of cells infected with S. Typhimurium. It is unclear whether this protein exerts a significant role in the progress of apoptosis and glycolysis in macrophages. Results: The S. Typhimurium SL1344 wild-type (WT) group, ΔsseK3 mutant group and sseK3-complemented group were used to infect macrophages and the effects of sseK3 on apoptosis and glycolysis of macrophages were investigated. The adherence and invasion of ΔsseK3 mutant group for macrophages were similar to WT group and sseK3-complemented group, indicating that SseK3 did not play an important role in the adherence and invasion of S. Typhimurium for macrophages. However, the apoptosis percentage of the ΔsseK3 mutant group was much lower than WT group and sseK3-complemented group using flow cytometry. The caspase-3, caspase-8 and caspase-9 enzyme activity of the ΔsseK3 mutant group were decreased significantly compared with WT group and sseK3-complemented group, which suggested that sseK3 could improve the activities of caspase-3, caspase-8 and caspase-9 enzyme. We also found that the pyruvic acid level did not significantly change among ΔsseK3 mutant group, WT group and sseK3-complemented group, but the lactic acid level of ΔsseK3 mutant group was much lower than WT group and sseK3-complemented group. The ATP level of ΔsseK3 mutant group was remarkably higher than WT group and sseK3-complemented group. These indicated that the sseK3 enhanced the level of glycolysis of macrophages infected by S. Typhimurium. Conclusions: Our data showed that the sseK3 of S. Typhimurium involved in promoting macrophages apoptosis and influencing glycolysis levels of macrophages. These results may give a better clue about the relationship between apoptosis and glycolysis in macrophages induced by S. Typhimurium sseK3.

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Thermodynamics in cancers: opposing interactions between PPAR gamma and the canonical WNT/beta‐catenin pathway

Cited by 65 publications

References 174 publications

Warburg effect hypothesis in autism Spectrum disorders

Warburg effect hypothesis in autism Spectrum disorders

Salmonella enterica serovar Typhimurium sseK3 induces apoptosis and enhances glycolysis in macrophages

The Salmonella enterica serovar Typhimurium sseK3 induce cell apoptosis and enhance glycolysis in macrophages

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