The Experts below are selected from a list of 60384 Experts worldwide ranked by ideXlab platform
Zhichao Wang - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate and aldolase mediate glucose sensing by ampk
Nature, 2017Co-Authors: Chensong Zhang, Simon A Hawley, Yue Zong, Mengqi Li, Zhichao Wang, Alexander Gray, Jinwei Feng, Yuqing Wu, Terytty Yang LiAbstract:Glucose starvation activates AMPK via an AMP/ADP-independent mechanism that involves fructose-1,6-bisphosphate and aldolase. AMPK is a central regulator of metabolic homeostasis, and its dysfunction may result in various diseases including diabetes, obesity, and cancer. AMPK is known to be activated under stressful conditions, including glucose starvation. It has been assumed that upon glucose deprivation AMPK activation occurs in the canonical AMP/ADP-dependent manner, with reduced metabolism of glucose causing falling ATP and increasing AMP and ADP. Here, Sheng-Cai Lin and colleagues show that this is not the case, and that glucose starvation activates AMPK via a different route, in an AMP/ADP-independent manner. During glycolysis, glucose is converted to fructose-1,6-bisphosphate (FBP), which is then processed by FBP aldolases. The authors show that the absence of glucose results in a reduction of FBP-bound aldolase, which triggers LKB1 phosphorylation and activation of AMPK. This study thus uncovers FBP as the critical metabolite that signals glucose availability and FBP aldolases as the sensors that relay the information to AMPK. The Major Energy Source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)1, but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK2,3,4,5. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation6,7. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
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fructose 1 6 bisphosphate and aldolase mediate glucose sensing by ampk
Nature, 2017Co-Authors: Chensong Zhang, Simon A Hawley, Yue Zong, Zhichao Wang, Alexander Gray, Jinwei Feng, Jiwen Cui, Mingjiang Zhu, Shuyong LinAbstract:The Major Energy Source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
Chensong Zhang - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate and aldolase mediate glucose sensing by ampk
Nature, 2017Co-Authors: Chensong Zhang, Simon A Hawley, Yue Zong, Mengqi Li, Zhichao Wang, Alexander Gray, Jinwei Feng, Yuqing Wu, Terytty Yang LiAbstract:Glucose starvation activates AMPK via an AMP/ADP-independent mechanism that involves fructose-1,6-bisphosphate and aldolase. AMPK is a central regulator of metabolic homeostasis, and its dysfunction may result in various diseases including diabetes, obesity, and cancer. AMPK is known to be activated under stressful conditions, including glucose starvation. It has been assumed that upon glucose deprivation AMPK activation occurs in the canonical AMP/ADP-dependent manner, with reduced metabolism of glucose causing falling ATP and increasing AMP and ADP. Here, Sheng-Cai Lin and colleagues show that this is not the case, and that glucose starvation activates AMPK via a different route, in an AMP/ADP-independent manner. During glycolysis, glucose is converted to fructose-1,6-bisphosphate (FBP), which is then processed by FBP aldolases. The authors show that the absence of glucose results in a reduction of FBP-bound aldolase, which triggers LKB1 phosphorylation and activation of AMPK. This study thus uncovers FBP as the critical metabolite that signals glucose availability and FBP aldolases as the sensors that relay the information to AMPK. The Major Energy Source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)1, but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK2,3,4,5. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation6,7. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
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fructose 1 6 bisphosphate and aldolase mediate glucose sensing by ampk
Nature, 2017Co-Authors: Chensong Zhang, Simon A Hawley, Yue Zong, Zhichao Wang, Alexander Gray, Jinwei Feng, Jiwen Cui, Mingjiang Zhu, Shuyong LinAbstract:The Major Energy Source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK), but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
Walter R Terra - One of the best experts on this subject based on the ideXlab platform.
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an insight into the transcriptome of the digestive tract of the bloodsucking bug rhodnius prolixus
PLOS Neglected Tropical Diseases, 2014Co-Authors: Jose M C Ribeiro, Fernando A Genta, Marcos Henrique Ferreira Sorgine, Raquel Logullo, Rafael D Mesquita, Gabriela O Paivasilva, David Majerowicz, Marcelo N Medeiros, Leonardo B Koerich, Walter R TerraAbstract:The bloodsucking hemipteran Rhodnius prolixus is a vector of Chagas' disease, which affects 7–8 million people today in Latin America. In contrast to other hematophagous insects, the triatomine gut is compartmentalized into three segments that perform different functions during blood digestion. Here we report analysis of transcriptomes for each of the segments using pyrosequencing technology. Comparison of transcript frequency in digestive libraries with a whole-body library was used to evaluate expression levels. All classes of digestive enzymes were highly expressed, with a predominance of cysteine and aspartic proteinases, the latter showing a significant expansion through gene duplication. Although no protein digestion is known to occur in the anterior midgut (AM), protease transcripts were found, suggesting secretion as pro-enzymes, being possibly activated in the posterior midgut (PM). As expected, genes related to cytoskeleton, protein synthesis apparatus, protein traffic, and secretion were abundantly transcribed. Despite the absence of a chitinous peritrophic membrane in hemipterans - which have instead a lipidic perimicrovillar membrane lining over midgut epithelia - several gut-specific peritrophin transcripts were found, suggesting that these proteins perform functions other than being a structural component of the peritrophic membrane. Among immunity-related transcripts, while lysozymes and lectins were the most highly expressed, several genes belonging to the Toll pathway - found at low levels in the gut of most insects - were identified, contrasting with a low abundance of transcripts from IMD and STAT pathways. Analysis of transcripts related to lipid metabolism indicates that lipids play multiple roles, being a Major Energy Source, a substrate for perimicrovillar membrane formation, and a Source for hydrocarbons possibly to produce the wax layer of the hindgut. Transcripts related to amino acid metabolism showed an unanticipated priority for degradation of tyrosine, phenylalanine, and tryptophan. Analysis of transcripts related to signaling pathways suggested a role for MAP kinases, GTPases, and LKBP1/AMP kinases related to control of cell shape and polarity, possibly in connection with regulation of cell survival, response of pathogens and nutrients. Together, our findings present a new view of the triatomine digestive apparatus and will help us understand trypanosome interaction and allow insights into hemipteran metabolic adaptations to a blood-based diet.
Terytty Yang Li - One of the best experts on this subject based on the ideXlab platform.
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fructose 1 6 bisphosphate and aldolase mediate glucose sensing by ampk
Nature, 2017Co-Authors: Chensong Zhang, Simon A Hawley, Yue Zong, Mengqi Li, Zhichao Wang, Alexander Gray, Jinwei Feng, Yuqing Wu, Terytty Yang LiAbstract:Glucose starvation activates AMPK via an AMP/ADP-independent mechanism that involves fructose-1,6-bisphosphate and aldolase. AMPK is a central regulator of metabolic homeostasis, and its dysfunction may result in various diseases including diabetes, obesity, and cancer. AMPK is known to be activated under stressful conditions, including glucose starvation. It has been assumed that upon glucose deprivation AMPK activation occurs in the canonical AMP/ADP-dependent manner, with reduced metabolism of glucose causing falling ATP and increasing AMP and ADP. Here, Sheng-Cai Lin and colleagues show that this is not the case, and that glucose starvation activates AMPK via a different route, in an AMP/ADP-independent manner. During glycolysis, glucose is converted to fructose-1,6-bisphosphate (FBP), which is then processed by FBP aldolases. The authors show that the absence of glucose results in a reduction of FBP-bound aldolase, which triggers LKB1 phosphorylation and activation of AMPK. This study thus uncovers FBP as the critical metabolite that signals glucose availability and FBP aldolases as the sensors that relay the information to AMPK. The Major Energy Source for most cells is glucose, from which ATP is generated via glycolysis and/or oxidative metabolism. Glucose deprivation activates AMP-activated protein kinase (AMPK)1, but it is unclear whether this activation occurs solely via changes in AMP or ADP, the classical activators of AMPK2,3,4,5. Here, we describe an AMP/ADP-independent mechanism that triggers AMPK activation by sensing the absence of fructose-1,6-bisphosphate (FBP), with AMPK being progressively activated as extracellular glucose and intracellular FBP decrease. When unoccupied by FBP, aldolases promote the formation of a lysosomal complex containing at least v-ATPase, ragulator, axin, liver kinase B1 (LKB1) and AMPK, which has previously been shown to be required for AMPK activation6,7. Knockdown of aldolases activates AMPK even in cells with abundant glucose, whereas the catalysis-defective D34S aldolase mutant, which still binds FBP, blocks AMPK activation. Cell-free reconstitution assays show that addition of FBP disrupts the association of axin and LKB1 with v-ATPase and ragulator. Importantly, in some cell types AMP/ATP and ADP/ATP ratios remain unchanged during acute glucose starvation, and intact AMP-binding sites on AMPK are not required for AMPK activation. These results establish that aldolase, as well as being a glycolytic enzyme, is a sensor of glucose availability that regulates AMPK.
Na Duan - One of the best experts on this subject based on the ideXlab platform.
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analysis of rural household Energy consumption and renewable Energy systems in zhangziying town of beijing
Ecological Modelling, 2015Co-Authors: Cong Lin, Yang Wang, Lingying Zhao, Na DuanAbstract:Rural Energy consumption significantly affects the economy of a country and plays a vital role in the rural residents’ lives. This paper analyzed the association of the rural household Energy consumption with their demands on renewable Energy systems and contributions to the reduction of CO2, TSP (total suspended particulate), and PM2.5 emissions in Zhangziying town of Daxing district of Beijing. This system analysis aimed to evaluate the sustainability of Energy supply and economic development in rural area of Beijing by taking Zhangziying town as an example. Specifically, in this paper Energy consumed by the rural households was investigated in terms of Energy Sources (coal, biogas, straw gas, LPG, electricity and firewood), utilization, choices, costs and systems. The results show that coal is still the Major Energy Source for heating during winter, which constitutes that largest portion of the household Energy consumption. With the development of renewable Energy, the utilization of coal, LPG and firewood for cooking has been replaced by renewable Energy such as biogas and straw gas, which are coupled with a higher heating value and lower price. Meanwhile, this study also suggests that the renewable Energy generated in the surveyed villages is equivalent to 32,863.68kgce and could annually reduce 81,929.15kgCO2 emissions, 22,347.30kg TSP, and 8938.92kg PM2.5 emissions. The structure of rural household Energy consumption of Zhangziying town is sustainable and environmentally sound. The structure of rural household Energy consumption is undergoing a transformation from traditional low-efficiency biomass domination to integrated consumption of traditional and renewable Energy Sources. Renewable Energy is not only a solution to the Energy shortage problem in rural areas, but also helps conserve fossil reSources and protect the environment.
