phosphatase activity
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2021 ◽  
Vol 2021 ◽  
pp. 1-11
Author(s):  
Xilin Xu ◽  
Yiwei Shen ◽  
Hang Lv ◽  
Jun Zhao ◽  
Xiaodong Li ◽  
...  

Steroid-induced osteonecrosis of the femoral head (SIONFH) is a frequent orthopedic disease caused by long-term or high-dose administration of corticosteroids. Tanshinone I (TsI), a flavonoid compound isolated from Salvia miltiorrhiza Bunge, has been reported to inhibit osteoclastic differentiation in vitro. This study aimed to investigate whether TsI can ameliorate SIONFH. Herein, SIONFH was induced by intraperitoneal injection of 20 μg/kg lipopolysaccharide every 24 h for 2 days, followed by an intramuscular injection of 40 mg/kg methylprednisolone every 24 h for 3 days. Four weeks after the final injection of methylprednisolone, the rats were intraperitoneally administrated with low-dose (5 mg/kg) and high-dose (10 mg/kg) TsI once daily for 4 weeks. Results showed that TsI significantly alleviated osteonecrotic lesions of the femoral heads as determined by micro-CT analysis. Furthermore, TsI increased alkaline phosphatase activity and expressions of osteoblastic markers including osteocalcin, type I collagen, osteopontin, and Runt-related transcription factor 2 and decreased tartrate-resistant acid phosphatase activity and expressions of osteoclastic markers including cathepsin K and acid phosphatase 5. TsI also reduced inflammatory response and oxidative stress and activated the nuclear factor erythroid 2-related factor 2 (Nrf2) signaling pathway in the femoral heads. Taken together, our findings show that TsI can relieve SIONFH, indicating that it may be a candidate for preventing SIONFH.


2021 ◽  
Vol 119 (1) ◽  
pp. e2110877119
Author(s):  
Yong Zhang ◽  
Jiaqi Fu ◽  
Shuxin Liu ◽  
Lidong Wang ◽  
Jiazhang Qiu ◽  
...  

Coxiella burnetii is a bacterial pathogen that replicates within host cells by establishing a membrane-bound niche called the Coxiella-containing vacuole. Biogenesis of this compartment requires effectors of its Dot/Icm type IV secretion system. A large cohort of such effectors has been identified, but the function of most of them remain elusive. Here, by a cell-based functional screening, we identified the effector Cbu0513 (designated as CinF) as an inhibitor of NF-κB signaling. CinF is highly similar to a fructose-1,6-bisphosphate (FBP) aldolase/phosphatase present in diverse bacteria. Further study reveals that unlike its ortholog from Sulfolobus tokodaii, CinF does not exhibit FBP phosphatase activity. Instead, it functions as a protein phosphatase that specifically dephosphorylates and stabilizes IκBα. The IκBα phosphatase activity is essential for the role of CinF in C. burnetii virulence. Our results establish that C. burnetii utilizes a protein adapted from sugar metabolism to subvert host immunity.


Biochemistry ◽  
2021 ◽  
Author(s):  
Jai Prakash Singh ◽  
Meng-Jung Lin ◽  
Shu-Fang Hsu ◽  
Wolfgang Peti ◽  
Cheng-Chung Lee ◽  
...  

2021 ◽  
Vol 23 (12) ◽  
pp. 270-284
Author(s):  
Kousalya. P ◽  
◽  
Doss VA ◽  

G-Protein Coupled Receptor (GPCR) plays a major role in cardiac hypertrophy. Isoproterenol is an agonist which binds to GPCR. This results in the activation of GS subunit. Activated Gs subunit stimulates cAMP mediated pathway. This activates the calcium signaling and elevates the calcium level. Increased calcium activates the phosphatase activity of calcineurin. Activated calcineurin dephosphorylates NFAT in cytoplasm. Dephosphorylated NFAT translocates to nucleus and binds to target region in DNA and activates re-expression of fetal genes in synergy with GATA-4 trascription factor. Reprogramming of fetal genes by NFAT- 3 and GATA-4 results in cardiac hypertrophy. Calcineurin inhibitors and rephosphorylation of NFAT can prevent cardiac hypertrophy.


2021 ◽  
Author(s):  
◽  
Grace Newson

<p>Scleractinian corals, which form the building blocks of tropical reefs, are reliant on a mutualistic symbiosis with phototrophic dinoflagellates of the family Symbiodiniaceae for their metabolic needs and survival. Unfortunately, when subjected to environmental stress this symbiosis can destabilise, culminating in coral bleaching (the loss of symbionts from coral tissue). The most prominent cause of coral bleaching is elevated sea surface temperatures as a result of global warming. However, local stressors such as eutrophication can determine coral reef resilience. Although the physiological responses to temperature and nutrient enrichment are well characterised, the cellular mechanisms underlying these responses are not well understood. This thesis aims to further the understanding of the physiological and cellular responses of Symbiodiniaceae to both thermal stress and nutrient availability.  The Symbiodiniaceae species used in this study was Breviolum minutum (ITS2 ‘type’ B1), the homologous symbiont of the model cnidarian Aiptasia. The first objective of this thesis was to compare the physiological response to a rapid versus slow temperature increase, in two strains of the Breviolum minutum (culture IDs: NZ01 and FlAp2), by measuring a range of physiological parameters in cultures exposed to an increase in temperature from 25 to 35°C, either immediately or over one-week. The physiological measurements taken were: population growth, chlorophyll fluorescence and concentration, photosynthetic and respiratory oxygen flux, and alkaline phosphatase activity (APA). Measurements of chlorophyll fluorescence and oxygen flux demonstrated that NZ01 was able to maintain photosynthetic efficiency and metabolic balance at 35˚C, while FlAp2 was experiencing lethal thermal stress. This divergence in physiological plasticity between strains was emphasised by different heating rates. FlAp2 showed more significant thermal stress at a slower heating rate, exemplified by reduced photosynthetic rates relative to cultures exposed to a rapid temperature increase. Alternately, NZ01 cultures exposed to a slow versus rapid heating rate demonstrated greater thermal acclimation, as alkaline phosphatase activity was elevated, and unlike cultures exposed to a rapid temperature increase, respiration and gross photosynthetic rates were equal to cultures at control temperatures. The intraspecies variability in thermal tolerance demonstrated in this thesis adds to the data supporting the intra-species physiological plasticity of the Symbiodiniaceae family.  The second objective of this thesis was to determine the influence of nutrient supply on the proteomic response to elevated temperature of B. minutum (using the FlAp2 strain). This was achieved by utilising novel proteomics techniques (Liquid chromatography-electrospray ionisation – tandem mass spectrometry, LC-ESI-MS/MS) and various physiological measurements to corroborate trends of protein expression (population growth, chlorophyll fluorescence and concentration, photosynthetic and respiratory oxygen flux, and alkaline phosphatase activity). Algal cultures were exposed to either ambient (dissolved inorganic nitrogen: DIN ~1.8 µM, dissolved inorganic phosphorus: DIP ~0.2 µM), imbalanced (DIN ~26 µM, DIP ~0.5 µM), or enriched nutrient regimes (DIN ~3 µM, DIP ~0.55 µM), at either 25 or 34˚C. Although it was hypothesised that there would be an interaction between the influence of temperature and nutrient availability on the Symbiodiniaceae proteome, this was not found. However, separately these environmental stressors had a strong influence on protein abundance. Temperature caused a reduction in photosynthesis proteins, ribosomal proteins, metabolic proteins (Calvin cycle/glycolysis) and proteins involved in biosynthesis, and a relative increased abundance of chaperonin proteins and proteins involved in cellular redox homeostasis.  Interestingly, the Symbiodiniaceae proteome under the ambient and enriched regimes was very similar, while the proteome under the imbalanced nutrient regime was different to these comparatively balanced regimes. This trend highlights the importance of the nitrogen to phosphorus ratio in determining the cellular response of Symbiodiniaceae to nutrient enrichment. Under an imbalanced nutrient regime, there was a down-regulation in photosynthetic and Calvin cycle proteins and an upregulation of proteins involved in protein translation, energy-generating metabolic pathways and storage-product turn-over. Consistent with previous studies, proteomic and physiological data indicated that B. minutum might have been experiencing phosphorus deficiency under an imbalanced nutrient regime. However, photochemical efficiency and metabolic balance was maintained, indicating metabolic adaption to the skewed nutrient ratio.  This thesis provides insight into the physiological and cellular response of Symbiodiniaceae to both temperature and nutrients, highlighting potential avenues of research that could be directed to facilitate the knowledge-based management of coral reefs. The intraspecies plasticity demonstrated in chapter two highlights the need to characterise physiological variability within Symbiodiniaceae species, as this could confer an adaptive advantage to the coral holobiont. In conjunction, the proteomics results of chapter three indicate that the relative availability of nitrogen to phosphorus determines the response of Sybiodiniaceae cellular physiology to nutrient availability. This emphasises the importance of determining the threshold of nitrogen to phosphorus that has a negative influence on the coral holobiont, facilitating the setting of ecologically relevant nutrient input limits by coral reef management.</p>


2021 ◽  
Author(s):  
◽  
Grace Newson

<p>Scleractinian corals, which form the building blocks of tropical reefs, are reliant on a mutualistic symbiosis with phototrophic dinoflagellates of the family Symbiodiniaceae for their metabolic needs and survival. Unfortunately, when subjected to environmental stress this symbiosis can destabilise, culminating in coral bleaching (the loss of symbionts from coral tissue). The most prominent cause of coral bleaching is elevated sea surface temperatures as a result of global warming. However, local stressors such as eutrophication can determine coral reef resilience. Although the physiological responses to temperature and nutrient enrichment are well characterised, the cellular mechanisms underlying these responses are not well understood. This thesis aims to further the understanding of the physiological and cellular responses of Symbiodiniaceae to both thermal stress and nutrient availability.  The Symbiodiniaceae species used in this study was Breviolum minutum (ITS2 ‘type’ B1), the homologous symbiont of the model cnidarian Aiptasia. The first objective of this thesis was to compare the physiological response to a rapid versus slow temperature increase, in two strains of the Breviolum minutum (culture IDs: NZ01 and FlAp2), by measuring a range of physiological parameters in cultures exposed to an increase in temperature from 25 to 35°C, either immediately or over one-week. The physiological measurements taken were: population growth, chlorophyll fluorescence and concentration, photosynthetic and respiratory oxygen flux, and alkaline phosphatase activity (APA). Measurements of chlorophyll fluorescence and oxygen flux demonstrated that NZ01 was able to maintain photosynthetic efficiency and metabolic balance at 35˚C, while FlAp2 was experiencing lethal thermal stress. This divergence in physiological plasticity between strains was emphasised by different heating rates. FlAp2 showed more significant thermal stress at a slower heating rate, exemplified by reduced photosynthetic rates relative to cultures exposed to a rapid temperature increase. Alternately, NZ01 cultures exposed to a slow versus rapid heating rate demonstrated greater thermal acclimation, as alkaline phosphatase activity was elevated, and unlike cultures exposed to a rapid temperature increase, respiration and gross photosynthetic rates were equal to cultures at control temperatures. The intraspecies variability in thermal tolerance demonstrated in this thesis adds to the data supporting the intra-species physiological plasticity of the Symbiodiniaceae family.  The second objective of this thesis was to determine the influence of nutrient supply on the proteomic response to elevated temperature of B. minutum (using the FlAp2 strain). This was achieved by utilising novel proteomics techniques (Liquid chromatography-electrospray ionisation – tandem mass spectrometry, LC-ESI-MS/MS) and various physiological measurements to corroborate trends of protein expression (population growth, chlorophyll fluorescence and concentration, photosynthetic and respiratory oxygen flux, and alkaline phosphatase activity). Algal cultures were exposed to either ambient (dissolved inorganic nitrogen: DIN ~1.8 µM, dissolved inorganic phosphorus: DIP ~0.2 µM), imbalanced (DIN ~26 µM, DIP ~0.5 µM), or enriched nutrient regimes (DIN ~3 µM, DIP ~0.55 µM), at either 25 or 34˚C. Although it was hypothesised that there would be an interaction between the influence of temperature and nutrient availability on the Symbiodiniaceae proteome, this was not found. However, separately these environmental stressors had a strong influence on protein abundance. Temperature caused a reduction in photosynthesis proteins, ribosomal proteins, metabolic proteins (Calvin cycle/glycolysis) and proteins involved in biosynthesis, and a relative increased abundance of chaperonin proteins and proteins involved in cellular redox homeostasis.  Interestingly, the Symbiodiniaceae proteome under the ambient and enriched regimes was very similar, while the proteome under the imbalanced nutrient regime was different to these comparatively balanced regimes. This trend highlights the importance of the nitrogen to phosphorus ratio in determining the cellular response of Symbiodiniaceae to nutrient enrichment. Under an imbalanced nutrient regime, there was a down-regulation in photosynthetic and Calvin cycle proteins and an upregulation of proteins involved in protein translation, energy-generating metabolic pathways and storage-product turn-over. Consistent with previous studies, proteomic and physiological data indicated that B. minutum might have been experiencing phosphorus deficiency under an imbalanced nutrient regime. However, photochemical efficiency and metabolic balance was maintained, indicating metabolic adaption to the skewed nutrient ratio.  This thesis provides insight into the physiological and cellular response of Symbiodiniaceae to both temperature and nutrients, highlighting potential avenues of research that could be directed to facilitate the knowledge-based management of coral reefs. The intraspecies plasticity demonstrated in chapter two highlights the need to characterise physiological variability within Symbiodiniaceae species, as this could confer an adaptive advantage to the coral holobiont. In conjunction, the proteomics results of chapter three indicate that the relative availability of nitrogen to phosphorus determines the response of Sybiodiniaceae cellular physiology to nutrient availability. This emphasises the importance of determining the threshold of nitrogen to phosphorus that has a negative influence on the coral holobiont, facilitating the setting of ecologically relevant nutrient input limits by coral reef management.</p>


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