RETRACTED: PFKFB3, a key glucose metabolic enzyme regulated by pathogen recognition receptor TLR4 in liver cells

Lu, Yan; Zhang, Lei; Zhu, Ran; Zhou, Hui-Juan; Fan, Huaying; Wang, Qiang

doi:10.1177/2042018820923474

Cited by 4 publications

(4 citation statements)

References 41 publications

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“…DNA topoisomerase 2-α (TOP2A) expression was restricted to the GCL. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263) – an enzyme involved in the control of glycolytic flux [ 29 ] appeared to be present in the OPL, likely in horizontal cells, as well as in the GCL. Finally, staining with the antibody directed against glutamate ionotropic receptor kainate 2 (GRIK2) confirmed its presence in the INL and GCL, in line with previous findings [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

et al. 2022

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Inherited retinal diseases (IRDs) are a group of neurodegenerative disorders that lead to photoreceptor cell death and eventually blindness. IRDs are characterised by a high genetic heterogeneity, making it imperative to design mutation-independent therapies. Mutations in a number of IRD disease genes have been associated with a rise of cyclic 3’,5’-guanosine monophosphate (cGMP) levels in photoreceptors. Accordingly, the cGMP-dependent protein kinase (PKG) has emerged as a new potential target for the mutation-independent treatment of IRDs. However, the substrates of PKG and the downstream degenerative pathways triggered by its activity have yet to be determined. Here, we performed kinome activity profiling of different murine organotypic retinal explant cultures (diseased rd1 and wild-type controls) using multiplex peptide microarrays to identify proteins whose phosphorylation was significantly altered by PKG activity. In addition, we tested the downstream effect of a known PKG inhibitor CN03 in these organotypic retina cultures. Among the PKG substrates were potassium channels belonging to the Kv1 family (KCNA3, KCNA6), cyclic AMP-responsive element-binding protein 1 (CREB1), DNA topoisomerase 2-α (TOP2A), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263), and the glutamate ionotropic receptor kainate 2 (GRIK2). The retinal expression of these PKG targets was further confirmed by immunofluorescence and could be assigned to various neuronal cell types, including photoreceptors, horizontal cells, and ganglion cells. Taken together, this study confirmed the key role of PKG in photoreceptor cell death and identified new downstream targets of cGMP/PKG signalling that will improve the understanding of the degenerative mechanisms underlying IRDs.

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Section: Resultsmentioning

confidence: 99%

Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

et al. 2022

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“…Gene array data showed upregulation of PFKFB1-3 in transgenic liver, a key enzyme regulating glucose metabolism and promoting aerobic glycolysis. Hence, previous publications have shown that inhibitors targeting PFKFB3 have been found to suppress aerobic glycolysis, decrease glucose uptake, and induce cancer cell autophagy [ 31 ]. Moreover, consistently with previous publications transgenic expression of c-MYC also enhances the expression of mitochondrial GL and GLS for canonical glutaminolysis.…”

Section: Discussionmentioning

confidence: 99%

A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy

Guo

Estévez-Vázquez

Benedé-Ubieto

et al. 2021

Cancers

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Background: Metabolic-associated fatty liver disease (MAFLD) has risen as one of the leading etiologies for hepatocellular carcinoma (HCC). Oncogenes have been suggested to be responsible for the high risk of MAFLD-related HCC. We analyzed the impact of the proto-oncogene c-MYC in the development of human and murine MAFLD and MAFLD-associated HCC. Methods: alb-myctg mice were studied at baseline conditions and after administration of Western diet (WD) in comparison to WT littermates. c-MYC expression was analyzed in biopsies of patients with MAFLD and MAFLD-associated HCC by immunohistochemistry. Results: Mild obesity, spontaneous hyperlipidaemia, glucose intolerance and insulin resistance were characteristic of 36-week-old alb-myctg mice. Middle-aged alb-myctg exhibited liver steatosis and increased triglyceride content. Liver injury and inflammation were associated with elevated ALT, an upregulation of ER-stress response and increased ROS production, collagen deposition and compensatory proliferation. At 52 weeks, 20% of transgenic mice developed HCC. WD feeding exacerbated metabolic abnormalities, steatohepatitis, fibrogenesis and tumor prevalence. Therapeutic use of metformin partly attenuated the spontaneous MAFLD phenotype of alb-myctg mice. Importantly, upregulation and nuclear localization of c-MYC were characteristic of patients with MAFLD and MAFLD-related HCC. Conclusions: A novel function of c-MYC in MAFLD progression was identified opening new avenues for preventative strategies.

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“…DNA topoisomerase 2-α (TOP2A) expression was restricted to the GCL. 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263) – an enzyme involved in the control of glycolytic flux (39) appeared to be present in the OPL, likely in horizontal cells, as well as in the GCL. Finally, staining with the antibody directed against glutamate ionotropic receptor kainate 2 (GRIK2) confirmed its presence in the INL and GCL, in line with previous findings (31).…”

Section: Resultsmentioning

confidence: 99%

“…DNA topoisomerase 2-α (TOP2A) expression was restricted to the GCL. 6phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263) -an enzyme involved in the control of glycolytic flux (39) appeared to be present in the OPL, likely in horizontal cells, as well as in the GCL.…”

Section: Pkg Target Validation For Retinal Localizationmentioning

confidence: 99%

Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

Roy

Tolone

Hilhorst

et al. 2021

Preprint

View full text Add to dashboard Cite

Inherited retinal diseases (IRDs) are a group of neurodegenerative disorders that lead to photoreceptor cell death and eventually blindness. IRDs are characterised by a high genetic heterogeneity, making it imperative to design mutation-independent therapies. Mutations in a number of IRD disease genes have been associated with a rise of cyclic 3',5'-guanosine monophosphate (cGMP) levels in photoreceptors. Accordingly, the cGMP-dependent protein kinase (PKG) has emerged as a new potential target for the mutation-independent treatment of IRDs. However, the substrates of PKG and the downstream degenerative pathways triggered by its activity have yet to be determined. Here, we performed kinome activity profiling of different murine organotypic retinal explant cultures (diseased rd1 and wild-type controls) using multiplex peptide microarrays to identify proteins whose phosphorylation was significantly altered by PKG activity. In addition, we tested the downstream effect of a known PKG inhibitor CN03 in these organotypic retina cultures. Among the PKG substrates were potassium channels belonging to the Kv1 family (KCNA3, KCNA6), Cyclic AMP-responsive element-binding protein 1 (CREB1), DNA topoisomerase 2-α (TOP2A), 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (F263), and the glutamate ionotropic receptor kainate 2 (GRIK2). The retinal expression of these PKG targets was further confirmed by immunofluorescence and could be assigned to various neuronal cell types, including photoreceptors, horizontal cells, and ganglion cells. Taken together, this study confirmed the key role of PKG in photoreceptor cell death and identified new downstream targets of cGMP/PKG signalling that will improve the understanding of the degenerative mechanisms underlying IRDs.

show abstract

RETRACTED: PFKFB3, a key glucose metabolic enzyme regulated by pathogen recognition receptor TLR4 in liver cells

Cited by 4 publications

References 41 publications

Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

A Shortcut from Metabolic-Associated Fatty Liver Disease (MAFLD) to Hepatocellular Carcinoma (HCC): c-MYC a Promising Target for Preventative Strategies and Individualized Therapy

Kinase activity profiling identifies putative downstream targets of cGMP/PKG signaling in inherited retinal neurodegeneration

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