Discover potential inhibitors for PFKFB3 using 3D-QSAR, virtual screening, molecular docking and molecular dynamics simulation

Bao, Yige; Zhou, Lu; Dai, Duoqian; Zhu, Xiaohong; Hu, Yanqiu; Qiu, Yaping

doi:10.1080/10799893.2018.1564150

Cited by 15 publications

(8 citation statements)

References 34 publications

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“…Finally, the absorbance was measured at 570 nm on a microplate reader (24072800, Thermo Fisher, United States). The experiment was repeated three times independently (Bao et al, 2018).…”

Section: Mtt Assaymentioning

confidence: 99%

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

et al. 2021

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Matrine, an active component of Sophora flavescens Ait root extracts, has been used in China for years to treat cancer and viral hepatitis. In the present study, we explored the effects of matrine on hyperglycemia-treated cardiomyocytes. Cardiomyocyte function, oxidative stress, cellular viability, and mitochondrial fusion were assessed through immunofluorescence, quantitative real-time PCR (qRT-PCR), enzyme-linked immunosorbent assays, and RNA interference. Matrine treatment suppressed hyperglycemia-induced oxidative stress in cardiomyocytes by upregulating transcription of nuclear factor erythroid 2-like 2 and heme oxygenase-1. Matrine also improved cardiomyocyte contractile and relaxation function during hyperglycemia, and it reduced hyperglycemia-induced cardiomyocyte death by inhibiting mitochondrial apoptosis. Matrine treatment increased the transcription of mitochondrial fusion-related genes and thus attenuated the proportion of fragmented mitochondria in cardiomyocytes. Inhibiting mitochondrial fusion by knocking down mitofusin 2 (Mfn2) abolished the cardioprotective effects of matrine during hyperglycemia. These results demonstrate that matrine could be an effective drug to alleviate hyperglycemia-induced cardiomyocyte damage by activating Mfn2-induced mitochondrial fusion.

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“…Finally, the absorbance was measured at 570 nm on a microplate reader (24072800, Thermo Fisher, United States). The experiment was repeated three times independently (Bao et al, 2018).…”

Section: Mtt Assaymentioning

confidence: 99%

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

et al. 2021

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“…Dulbecco's modified Eagle's medium (DMEM)-F12 medium (Thermo Fisher Scientific, Shanghai, China) containing 10% fetal bovine serum (FBS) and 1% penicillin and streptomycin were used for cell culture. When the cells were 80% confluent, 0.25% trypsin (Thermo Fisher HyClone, Utah, United States) was used for cell trypsinization and passage (Bao et al, 2018). Cells in the logarithmic growth phase were selected for later use.…”

Section: Cell Culture and Treatmentmentioning

confidence: 99%

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Liu

Huang

2020

Front. Cell Dev. Biol.

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Mitochondria are potential targets for the treatment of cardio-cerebrovascular ischemiareperfusion (I/R) injury. However, the role of the mitofusin 2 (Mfn2) protein in regulating mitochondrial fusion and cell survival has not been investigated. In the present study, an adenovirus-mediated Mfn2 overexpression assay was performed to understand the effects of Mfn2 on mitochondrial function and cell damage during cardiocerebrovascular I/R injury. After exposure to I/R injury in vitro, the transcription and expression of Mfn2 were significantly downregulated, which correlated with decreased cell viability and increased apoptosis. By contrast, overexpression of Mfn2 significantly repressed I/R-mediated cell death through modulation of glucose metabolism and oxidative stress. Furthermore, Mfn2 overexpression improved mitochondrial fusion in cells, an effect that was followed by increased mitochondrial membrane potential, improved mitophagy, and inhibition of mitochondria-mediated apoptosis. Our data also demonstrated that Mfn2 overexpression was associated with activation of the AMPK/Sirt3 signaling pathway. Inhibition of the AMPK/Sirt3 pathway abolished the protective effects of Mfn2 on I/R-induced cell injury arising from mitochondrial damage. Our results indicate that Mfn2 protects against cardio-cerebrovascular I/R injury by augmenting mitochondrial fusion and activating the AMPK/Sirt3 signaling pathway.

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“…Because the PFK-1 A subunit has more similar reaction conformations than the B subunit, molecular dynamics simulations were performed on a globular protein constructed of a PFK-1 (PDB entry 1PFK) A subunit, referred to as a many species structure 1 , 15 , 45 , 55 , 56 , in of dilute aqueous solution. MD simulations were performed with the AMBER 14 package 57 using a 0.1 ps integration time step and periodic boundary conditions with the 124 × 115 × 131 Å 3 box.…”

Section: Methodsmentioning

confidence: 99%

Temperature effect on water dynamics in tetramer phosphofructokinase matrix and the super-arrhenius respiration rate

Yang

et al. 2021

Sci Rep

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Advances in understanding the temperature effect on water dynamics in cellular respiration are important for the modeling of integrated energy processes and metabolic rates. For more than half a century, experimental studies have contributed to the understanding of the catalytic role of water in respiration combustion, yet the detailed water dynamics remains elusive. We combine a super-Arrhenius model that links the temperature-dependent exponential growth rate of a population of plant cells to respiration, and an experiment on isotope labeled 18O2 uptake to H218O transport role and to a rate-limiting step of cellular respiration. We use Phosphofructokinase (PFK-1) as a prototype because this enzyme is known to be a pacemaker (a rate-limiting enzyme) in the glycolysis process of respiration. The characterization shows that PFK-1 water matrix dynamics are crucial for examining how respiration (PFK-1 tetramer complex breathing) rates respond to temperature change through a water and nano-channel network created by the enzyme folding surfaces, at both short and long (evolutionary) timescales. We not only reveal the nano-channel water network of PFK-1 tetramer hydration topography but also clarify how temperature drives the underlying respiration rates by mapping the channels of water diffusion with distinct dynamics in space and time. The results show that the PFK-1 assembly tetramer possesses a sustainable capacity in the regulation of the water network toward metabolic rates. The implications and limitations of the reciprocal-activation–reciprocal-temperature relationship for interpreting PFK-1 tetramer mechanisms are briefly discussed.

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Discover potential inhibitors for PFKFB3 using 3D-QSAR, virtual screening, molecular docking and molecular dynamics simulation

Cited by 15 publications

References 34 publications

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

RETRACTED: Matrine Protects Cardiomyocytes Against Hyperglycemic Stress by Promoting Mitofusin 2-Induced Mitochondrial Fusion

RETRACTED: Mfn2 Overexpression Attenuates Cardio-Cerebrovascular Ischemia–Reperfusion Injury Through Mitochondrial Fusion and Activation of the AMPK/Sirt3 Signaling

Temperature effect on water dynamics in tetramer phosphofructokinase matrix and the super-arrhenius respiration rate

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