细胞能量代谢改变可以激活腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK),氧化应激同样也能激活AMPK,参与机体抗氧化还原反应的调节。综述AMPK与氧化应激及其与运动关系的最新研究进展,以期为慢性病的形成、防治以及运动性疲...细胞能量代谢改变可以激活腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK),氧化应激同样也能激活AMPK,参与机体抗氧化还原反应的调节。综述AMPK与氧化应激及其与运动关系的最新研究进展,以期为慢性病的形成、防治以及运动性疲劳的发生机制等相关领域的研究提供理论依据。展开更多
As a member of an important group of lipid soluble antioxidants, tocopherols play a paramount role in the daily diet of humans and animals. Recently, genes required for tocochromanol biosynthesis pathway have been ide...As a member of an important group of lipid soluble antioxidants, tocopherols play a paramount role in the daily diet of humans and animals. Recently, genes required for tocochromanol biosynthesis pathway have been identified and cloned with the help of genomics-based approaches and molecular manipulation in the model organisms： Arabidopsis thaliana and Synechocystis sp. PCC 6803. At the basis of these foundations, genetic manipulation of tocochromanol biosynthesis pathway can give rise to strategies that enhance the level of tocochromanol content or convert the constitution of tocochromanol. In addition, genetic manipulations of the tocochromanol biosynthesis pathway provide help for the study of the function of tocopherol in plant systems. The present article summarizes recent advances and pays special attention to the functions of tocopherol in plants. The roles of tocopherol in the network of reactiv.e oxygen species, antioxidants and phytohormones to maintain redox homeostasis and the functions of tocopherol as a signal molecule in chloroplast-to- nucleus signaling to regulate carbohydrate metabolism are also discussed.展开更多
PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expr...PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.展开更多
Product yield on carbohydrate feedstocks is a key performance indicator for industrial ethanol production with the yeast Saccharomyces cerevisiae.This paper reviews pathway engineering strategies for improving ethanol...Product yield on carbohydrate feedstocks is a key performance indicator for industrial ethanol production with the yeast Saccharomyces cerevisiae.This paper reviews pathway engineering strategies for improving ethanol yield on glucose and/or sucrose in anaerobic cultures of this yeast by altering the ratio of ethanol production,yeast growth and glycerol formation.Particular attention is paid to strategies aimed at altering energy coupling of alcoholic fermentation and to strategies for altering redox-cofactor coupling in carbon and nitrogen meta-bolism that aim to reduce or eliminate the role of glycerol formation in anaerobic redox metabolism.In addition to providing an overview of scientific advances we discuss context dependency,theoretical impact and potential for industrial application of different proposed and developed strategies.展开更多
Butanol is a promising biofuel with high energy intensity and can be used as gasoline substitute. It can be produced as a sustainable energy by microorganisms （such as Clostridia） from low-value biomass. However, th...Butanol is a promising biofuel with high energy intensity and can be used as gasoline substitute. It can be produced as a sustainable energy by microorganisms （such as Clostridia） from low-value biomass. However, the low productivity, yield and selectivity in butanol fermentation are still big challenges due to the lack of an efficient butanol-producing host strain. In this article, we systematically review the host cell engineering of Clostridia, focusing on （1） various strategies to rebalance metabolic flux to achieve a high butanol production by regulating the metabolism of carbon, redox or energy, （2） the challenges in pathway manipulation, and （3） the application of proteomics technology to understand the intracellular metabolism. In addition, the process engineer- ing is also briefly described. The objective of this review is to summarize the previous research achievements in the metabolic engineering of Clostridium and provide guidance for future novel strain construction to effectively produce butanol.展开更多
Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes dep...Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.展开更多
The involvement of mitochondrial dysfunction in many pathophysiological conditions and human diseases is well documented.In order to evaluate mitochondrial function in vitro,many experimental systems have been develop...The involvement of mitochondrial dysfunction in many pathophysiological conditions and human diseases is well documented.In order to evaluate mitochondrial function in vitro,many experimental systems have been developed.Nevertheless the number of in vivo monitoring systems for the evaluation of mitochondrial activities in intact animals and patients is relatively limited.The pioneering development of the conceptual and technological aspects ofmitochondrial monitoring,in vitro and in vivo,was done by the late Prof.Britton Chance(July 24,1913November 16,2010)since the early 1950s.It was my privilege to join his laboratory in 1972 and collaborate with him for almost four decades.The main achievements of our collaboration are presented in this paper.Our activities included cycles of technology development,followed by its applications to study various pathophysiological conditions.In the initial stage,thefirstfiber-opticbased NADHfluorometer was developed.This device enabled us to monitor various organs in anesthetized animals aswell as the brain of nonanesthetized small animals.Later on,the addition of various physiological parameters to NADH monitoring enabled us to correlate mitochondrial function with other cellular functions.The application of the developed technology to clinical situations was a major interest of Prof.Chance and indeed this goal was achieved in the last decade.As of today,the basic tool forNADHmonitoring and the large database of results are available for large-scale experimental and clinical applications.展开更多
Integrins,over-expressed in a broad range of cancer diseauses,are widely utilized as a tumor biomarker.Metabolism investigation also plays important roles in tumor theranostics.Devel-oping simple integrin-targetting p...Integrins,over-expressed in a broad range of cancer diseauses,are widely utilized as a tumor biomarker.Metabolism investigation also plays important roles in tumor theranostics.Devel-oping simple integrin-targetting probe and monitoring tumor metabolism will give opportunities to find ways for cancer treatment,however,the investigation of tumor metabolism with integrin receptor based probes has been rarely reported so far.Here,we developed an octavalent fuo-rescent probe Octa-R.GD by convenient genetic method,based on one tetrameric far-red fluo-rescent protein(fRFP)linked with RGD pept ides.We validated its inter gin targeting by confocal imaging in vitro.Then we screened a variety of tumor cells,and differentiated their binding affinity based on the fuorescence of the probe via flow cytometry.Among these cells,CNE-2 cells had the highest uptake of the probe,while B16 cells had the lowest,corresponding with their intergin expression levels.Next,the fuorescent and metabolic imaging was performed in HT1080(intergin postive)tumor,where nicotinamide adenine dinudeotide hydrogen(NADH),flavo-protein(Fp)and fRFP fuorescent signals were collected.The tumor from mice intravenously injected with Octa RGD probe displayed obviously higher NADH redox ratio NADH/(Fp+NADH)and fRFP signal,than those with fRFP protein.It suggested that integrin targeting may have influence on the target cell metabolism,and further demonstrated Octa-R.GD probe facilitated its uptake in the targeted tumor in vrivo.This paper developed a useful probe,which can bind integrins speci-cally and e±ciently in tumor cells,and together with tumor metabolic information,it may provide new insight for RGD targeting-based cancer therapeutics.展开更多
Dear Editor, Arsenic (As) is a harmful metalloid that occurs in soil and water;its concentration varies considerably among geographic regions, with groundwater being the principal source of human contamination (Smedle...Dear Editor, Arsenic (As) is a harmful metalloid that occurs in soil and water;its concentration varies considerably among geographic regions, with groundwater being the principal source of human contamination (Smedley and Kinniburgh, 2002). Besides the direct contamination effect of drinking water that contains high As concentration, human poisoning may also occur after ingestion of contaminated food.展开更多
文摘细胞能量代谢改变可以激活腺苷酸活化蛋白激酶(AMP-activated protein kinase,AMPK),氧化应激同样也能激活AMPK,参与机体抗氧化还原反应的调节。综述AMPK与氧化应激及其与运动关系的最新研究进展,以期为慢性病的形成、防治以及运动性疲劳的发生机制等相关领域的研究提供理论依据。
基金the State Key Basic Research and Development Program of China (973 Program, 2007CB108805)
文摘As a member of an important group of lipid soluble antioxidants, tocopherols play a paramount role in the daily diet of humans and animals. Recently, genes required for tocochromanol biosynthesis pathway have been identified and cloned with the help of genomics-based approaches and molecular manipulation in the model organisms： Arabidopsis thaliana and Synechocystis sp. PCC 6803. At the basis of these foundations, genetic manipulation of tocochromanol biosynthesis pathway can give rise to strategies that enhance the level of tocochromanol content or convert the constitution of tocochromanol. In addition, genetic manipulations of the tocochromanol biosynthesis pathway provide help for the study of the function of tocopherol in plant systems. The present article summarizes recent advances and pays special attention to the functions of tocopherol in plants. The roles of tocopherol in the network of reactiv.e oxygen species, antioxidants and phytohormones to maintain redox homeostasis and the functions of tocopherol as a signal molecule in chloroplast-to- nucleus signaling to regulate carbohydrate metabolism are also discussed.
基金support by the Ministerio Educación y CienciaMinisterio de Economía y Competitividad of Spain(until June 2013)
文摘PDRG1 is a small oncogenic protein of 133 residues. In normal human tissues, the p53 and DNA damageregulated gene 1(PDRG1) gene exhibits maximal expression in the testis and minimal levels in the liver. Increased expression has been detected in several tumor cells and in response to genotoxic stress. High-throughput studies identified the PDRG1 protein in a variety of macromolecular complexes involved in processes that are altered in cancer cells. For example, this oncogene has been found as part of the RNA polymerase Ⅱ complex, the splicing machinery and nutrient sensing machinery, although its role in these complexes remains unclear. More recently, the PDRG1 protein was found as an interaction target for the catalytic subunits of methionine adenosyltransferases. These enzymes synthesize S-adenosylmethionine, the methyl donor for, among others, epigenetic methylations that occur on the DNA and histones. In fact, downregulation of S-adenosylmethionine synthesis is the first functional effect directly ascribed to PDRG1. The existence of global DNA hypomethylation, together with increased PDRG1 expression, in many tumor cells highlights the importance of this interaction as one of the putative underlying causes for cell transformation. Here, we will review the accumulated knowledge on this oncogene, emphasizing the numerous aspects that remain to be explored.
文摘Product yield on carbohydrate feedstocks is a key performance indicator for industrial ethanol production with the yeast Saccharomyces cerevisiae.This paper reviews pathway engineering strategies for improving ethanol yield on glucose and/or sucrose in anaerobic cultures of this yeast by altering the ratio of ethanol production,yeast growth and glycerol formation.Particular attention is paid to strategies aimed at altering energy coupling of alcoholic fermentation and to strategies for altering redox-cofactor coupling in carbon and nitrogen meta-bolism that aim to reduce or eliminate the role of glycerol formation in anaerobic redox metabolism.In addition to providing an overview of scientific advances we discuss context dependency,theoretical impact and potential for industrial application of different proposed and developed strategies.
文摘Butanol is a promising biofuel with high energy intensity and can be used as gasoline substitute. It can be produced as a sustainable energy by microorganisms （such as Clostridia） from low-value biomass. However, the low productivity, yield and selectivity in butanol fermentation are still big challenges due to the lack of an efficient butanol-producing host strain. In this article, we systematically review the host cell engineering of Clostridia, focusing on （1） various strategies to rebalance metabolic flux to achieve a high butanol production by regulating the metabolism of carbon, redox or energy, （2） the challenges in pathway manipulation, and （3） the application of proteomics technology to understand the intracellular metabolism. In addition, the process engineer- ing is also briefly described. The objective of this review is to summarize the previous research achievements in the metabolic engineering of Clostridium and provide guidance for future novel strain construction to effectively produce butanol.
基金This work is funded by National Natural Science Foundation of China(No.81773466)to W.H,and by Beijing Key Laboratory of Metabolic Disorder Related Cardiovascular Disease(No.DXWL2023-06)to W.X.
文摘Epigenetic modifications modulate conformational structure of chromatin and consequently gene expression by enzyme-mediated chemical modifications of DNA and histones.The activities of epigenetic modifying enzymes depend on many co-substrates and cofactors,such as 2-oxoglutarate(2-OG),iron,S-adenosylmethionine(SAM),nicotinamide adenine dinucleotide(NAD+),flavin adenine dinucleotide(FAD),and acetyl-CoA.These factors are inter-connecting molecules that integrate cellular nutrient metabolism and redox homeostasis,two key regulators of cell proliferation,cell survival,and cell functions.Dysregulation of such delicate regulatory network has been implicated in many pathological conditions and also been increasingly recognized as an emerging mechanism responsible for environmental pollutant-induced adverse effects.In this review,we first summarize DNA and histone modifying enzymes and their essential factors,then discuss the metabolic sources and the redox regulatory roles of these enzymatic factors,and finally elaborate the mechanisms of how targeting such factors by environmental pollutants influences epigenetic regulation and perturbs cellular functions.
文摘The involvement of mitochondrial dysfunction in many pathophysiological conditions and human diseases is well documented.In order to evaluate mitochondrial function in vitro,many experimental systems have been developed.Nevertheless the number of in vivo monitoring systems for the evaluation of mitochondrial activities in intact animals and patients is relatively limited.The pioneering development of the conceptual and technological aspects ofmitochondrial monitoring,in vitro and in vivo,was done by the late Prof.Britton Chance(July 24,1913November 16,2010)since the early 1950s.It was my privilege to join his laboratory in 1972 and collaborate with him for almost four decades.The main achievements of our collaboration are presented in this paper.Our activities included cycles of technology development,followed by its applications to study various pathophysiological conditions.In the initial stage,thefirstfiber-opticbased NADHfluorometer was developed.This device enabled us to monitor various organs in anesthetized animals aswell as the brain of nonanesthetized small animals.Later on,the addition of various physiological parameters to NADH monitoring enabled us to correlate mitochondrial function with other cellular functions.The application of the developed technology to clinical situations was a major interest of Prof.Chance and indeed this goal was achieved in the last decade.As of today,the basic tool forNADHmonitoring and the large database of results are available for large-scale experimental and clinical applications.
基金supported by the Major Research plan of the National Natural Science Foundation of China(Grant No.91442201)the China Postdoctoral Science Foundation funded project(Grant Nos.2015M572148,2012M521430 and 2013T60721)the Open Research Fund of State Key Laboratory of Bioelectronics of Southeast University.Shuang Sha and Fei Yang contributed equally to this work.
文摘Integrins,over-expressed in a broad range of cancer diseauses,are widely utilized as a tumor biomarker.Metabolism investigation also plays important roles in tumor theranostics.Devel-oping simple integrin-targetting probe and monitoring tumor metabolism will give opportunities to find ways for cancer treatment,however,the investigation of tumor metabolism with integrin receptor based probes has been rarely reported so far.Here,we developed an octavalent fuo-rescent probe Octa-R.GD by convenient genetic method,based on one tetrameric far-red fluo-rescent protein(fRFP)linked with RGD pept ides.We validated its inter gin targeting by confocal imaging in vitro.Then we screened a variety of tumor cells,and differentiated their binding affinity based on the fuorescence of the probe via flow cytometry.Among these cells,CNE-2 cells had the highest uptake of the probe,while B16 cells had the lowest,corresponding with their intergin expression levels.Next,the fuorescent and metabolic imaging was performed in HT1080(intergin postive)tumor,where nicotinamide adenine dinudeotide hydrogen(NADH),flavo-protein(Fp)and fRFP fuorescent signals were collected.The tumor from mice intravenously injected with Octa RGD probe displayed obviously higher NADH redox ratio NADH/(Fp+NADH)and fRFP signal,than those with fRFP protein.It suggested that integrin targeting may have influence on the target cell metabolism,and further demonstrated Octa-R.GD probe facilitated its uptake in the targeted tumor in vrivo.This paper developed a useful probe,which can bind integrins speci-cally and e±ciently in tumor cells,and together with tumor metabolic information,it may provide new insight for RGD targeting-based cancer therapeutics.
基金supported by Secretaría de Ciencia y Técnica de la Universidad Nacional de Río Cuarto(SECYT-UNRC)Consejo Nacional de Investigaciones Científicas y Técnicas(CONICET),Argentinafunded by the Spanish Ministry of Economy and Competitiveness(Awarded to the author L.E.Hernández’s projects AGL2010-15151 and AGL2014-53771-R)
文摘Dear Editor, Arsenic (As) is a harmful metalloid that occurs in soil and water;its concentration varies considerably among geographic regions, with groundwater being the principal source of human contamination (Smedley and Kinniburgh, 2002). Besides the direct contamination effect of drinking water that contains high As concentration, human poisoning may also occur after ingestion of contaminated food.
