Locoweed is a poisonous plant that severely harms the development of grass-land and animal husbandry throughout the world. Oxytropis and Astragalus are the Latin names for the poisonous plants commonly known as locowe...Locoweed is a poisonous plant that severely harms the development of grass-land and animal husbandry throughout the world. Oxytropis and Astragalus are the Latin names for the poisonous plants commonly known as locoweed. The main toxic substance in these plants is swainsonine. It is a strong inhibitor of lysosomal α-mannosidase I and Golgi body α-mannosidase II, resulting in the accumulation of oligosaccharides and glycoproteins in lysosomes, interfering with the molecular and cellular recognition of glycans, and causing tissue-cell vacuolar degeneration. Livestock shows a series of clinical and pathological symptoms, mainly for the decline of reproductive performance. The effects in dams are abortion, weak fetus, and fetal malformations. The key step in maintaining pregnancy in dams is early endometrial decidualization, because reproductive hormones, decidual cell apoptosis, endoplasmic reticulum (ER) stress, and other immune factors are negatively affected by swainsonine. This article addresses the modifications that occur through glycan processing and glycosylation resulting in the change of post-translational modification of the protein and the activity of the glycoprotein, and then direct and indirect mechanisms of ER stress, apoptosis, reproductive hormones, immune factors, and cell cycle and other pathways. Our aim is to find new methods of prevention and treatment of swainsonine poisoning in grassland animals.展开更多
The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to th...The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.展开更多
It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular ...It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.展开更多
The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the ad...The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma.OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL 2,respectively.The relationship between pathological and clinical factors of patients was analyzed.We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues.RL 2 antibody level was positively correlated with OGT expression,and the metastasis of lymph node,which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma.In conclusion,OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma.O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.展开更多
Comprehensive Summary The strategy of removable glycosylation modification was used to overcome the low-efficiency problem encountered in the chemical synthesis of the mirror-image D-version of the immunoglobulin(Ig)-...Comprehensive Summary The strategy of removable glycosylation modification was used to overcome the low-efficiency problem encountered in the chemical synthesis of the mirror-image D-version of the immunoglobulin(Ig)-like domain of tropomyosin receptor kinase A(DlgCTrkA),a protein molecule needed for mirror-image screening of D-peptide ligands targeting this cell membrane receptor.It was found that O-linked-β-N-acetyl-D-glucosamine(O-GlcNAc)modification at^(D)Ser^(312),or^(D)Ser^(320)can significantly improve the efficiency of DlgCTrkA synthesis and folding,while O-GlcNAc modification at^(D)Ser^(330)showed barely any improvement.This study provides a new example demonstrating the power of the removable glycosylation modification strategy in the chemical synthesis and folding of difficult-to-obtain proteins.It also presents evidence that removable glycosylation modification at different sites would significantly affect the efficiency of protein folding promoted by this strategy.展开更多
Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial activity.Precisely adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulatin...Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial activity.Precisely adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulating bacterial behavior,but has been proven to be difficult.Herein,surface topological glycosylation is reported to mediate the interaction of bacteria with mucous layer.Alkynes functionalized by sugar moieties with different branching are synthesized through iterative Michael addition and amide condensation reactions.By a copper-catalyzed azide-alkyne cycloaddition,the resulting compounds with different branching structures can be attached onto bacterial surface that is modified with azido groups.As a proof-of-concept study,a set of topologically glycosylated probiotics(TGPs)is prepared using linear,two-branched,and tetra-branched compounds,respectively.The interaction between mucin and TGPs was studied and the results demonstrate that,compared to unmodified bacteria,TGPs exhibit an enhanced adhesive capacity to mucin,which increases with the branching numbers.Similar binding trend is observed in ex vivo colonic mucus adhesion experiments and bacteria glycosylated with tetra-branched compounds display the highest binding efficiency.This work proposes a chemical method to tune the abundance and distribution of sugar moieties on bacteria,providing unique significant insights into the manipulation of bacterial behavior through surface modification.展开更多
利用转谷氨酰胺酶(transglutaminase,TGase)催化玉米醇溶蛋白与氨基葡萄糖盐酸盐(glucosamine hydrochloride,GAH)发生交联反应。通过SDS-聚丙烯酰胺凝胶电泳确认玉米醇溶蛋白与GAH发生交联反应。以玉米醇溶蛋白糖基化修饰产物中GAH导...利用转谷氨酰胺酶(transglutaminase,TGase)催化玉米醇溶蛋白与氨基葡萄糖盐酸盐(glucosamine hydrochloride,GAH)发生交联反应。通过SDS-聚丙烯酰胺凝胶电泳确认玉米醇溶蛋白与GAH发生交联反应。以玉米醇溶蛋白糖基化修饰产物中GAH导入量为指标,优化糖基化反应条件,并对玉米醇溶蛋白糖基化修饰样品的溶解性进行了表征。结果表明,最适的糖基化反应条件为底物质量浓度5 g/100 m L、TGase添加量50 U/g(以玉米醇溶蛋白计)、玉米醇溶蛋白中酰基供体与GAH中的酰基受体物质的量比1∶6、初始p H 8.0、反应温度44℃、反应时间7 h;此反应条件下,玉米醇溶蛋白中GAH的最大导入量为(11.34±0.21)mg/g(以玉米醇溶蛋白计)。与玉米醇溶蛋白相比,玉米醇溶蛋白交联样品与糖基化修饰样品的溶解性均得到提高,玉米醇溶蛋白糖基化修饰样品的溶解性最高。展开更多
文摘Locoweed is a poisonous plant that severely harms the development of grass-land and animal husbandry throughout the world. Oxytropis and Astragalus are the Latin names for the poisonous plants commonly known as locoweed. The main toxic substance in these plants is swainsonine. It is a strong inhibitor of lysosomal α-mannosidase I and Golgi body α-mannosidase II, resulting in the accumulation of oligosaccharides and glycoproteins in lysosomes, interfering with the molecular and cellular recognition of glycans, and causing tissue-cell vacuolar degeneration. Livestock shows a series of clinical and pathological symptoms, mainly for the decline of reproductive performance. The effects in dams are abortion, weak fetus, and fetal malformations. The key step in maintaining pregnancy in dams is early endometrial decidualization, because reproductive hormones, decidual cell apoptosis, endoplasmic reticulum (ER) stress, and other immune factors are negatively affected by swainsonine. This article addresses the modifications that occur through glycan processing and glycosylation resulting in the change of post-translational modification of the protein and the activity of the glycoprotein, and then direct and indirect mechanisms of ER stress, apoptosis, reproductive hormones, immune factors, and cell cycle and other pathways. Our aim is to find new methods of prevention and treatment of swainsonine poisoning in grassland animals.
基金Supported by Ministerio de Ciencia Innovación y Universidades,No.SAF2017-82436R and SAF2016-75004RComunidad de Madrid,No.S2017/BMD-3686+2 种基金Fundación Ramón Areces,No.2016/CIVP18A3864Instituto de Salud Carlos Ⅲby Fondos FEDER,No.Cibercv and Ciberehd
文摘The biosynthesis of prostanoids is involved in both physiological and pathological processes. The expression of prostaglandin-endoperoxide synthase 2(PTGS2; also known as COX-2) has been traditionally associated to the onset of several pathologies, from inflammation to cardiovascular, gastrointestinal and oncologic events. For this reason, the search of selective PTGS2 inhibitors has been a focus for therapeutic interventions. In addition to the classic non-steroidal anti-inflammatory drugs, selective and specific PTGS2 inhibitors, termed coxibs, have been generated and widely used. PTGS2 activity is less restrictive in terms of substrate specificity than the homeostatic counterpart PTGS1, and it accounts for the elevated prostanoid synthesis that accompanies several pathologies. The main regulation of PTGS2 occurs at the transcription level. In addition to this, the stability of the mRNA is finely regulated through the interaction with several cytoplasmic elements, ranging from specificmicroR NAs to proteins that control mR NA degradation. Moreover, the protein has been recognized to be the substrate for several post-translational modifications that affect both the enzyme activity and the targeting for degradation via proteasomal and non-proteasomal mechanisms. Among these modifications, phosphorylation, glycosylation and covalent modifications by reactive lipidic intermediates and by free radicals associated to the proinflammatory condition appear to be the main changes. Identification of these post-translational modifications is relevant to better understand the role of PTGS2 in several pathologies and to establish a correct analysis of the potential function of this protein in diseases progress. Finally, these modifications can be used as biomarkers to establish correlations with other parameters, including the immunomodulation dependent on molecular pathological epidemiology determinants, which may provide a better frame for potential therapeutic interventions.
文摘It is likely that the majority of proteins will undergo post-translational modification, be it enzymatic or non-enzymatic. These modified protein(s) regulate activity, localization and interaction with other cellular molecules thereby maintaining cellular hemostasis. Alcohol exposure significantly alters several of these post-translational modifications leading to impairments of many essential physiological processes. Here, we present new insights into novel modifications following ethanol exposure and their role in the initiation and progression of liver injury. This critical review condenses the proceedings of a symposium at the European Society for the Biomedical Research on Alcoholism Meeting held September 12-15, 2015, in Valencia, Spain.
文摘The aim of this present study was to explore the expression and clinical significance of O-linked N-acetylglucosamine（O-GlcNAc） transferase（OGT） and enzymatic O-linked glycosylation（O-GlcNAcation） through the addition of O-linked-β-N-acetylglucosamine in esophageal squamous cell carcinoma.OGT expression and O-GlcNAcation in 40 samples from patients with esophageal squamous cell carcinoma was detected by immunohistochemical staining with anti-OGT antib ody and O-GlcNAc-specific antibody RL 2,respectively.The relationship between pathological and clinical factors of patients was analyzed.We found that the expression of OGT was higher in esophageal squamous cell carcinoma samples compared to the normal tissues.RL 2 antibody level was positively correlated with OGT expression,and the metastasis of lymph node,which means the level of O-GlcNAcation was high and related to the metastasis of lymph node in esophageal squamous cell carcinoma.In conclusion,OGT activation is the main reason for promoting the level of O-GlcNAcation in esophageal squamous cell carcinoma.O-GlcNAcylation may play an important role in esophageal squamous cell carcinoma.
基金supported by the National Natural Science Foundation of China(Nos.22227810,22277020,22307061)China Postdoctoral Science Foundation(No.2022M721801)the Beijing Life Science Academy(No.2023000cc0130).
文摘Comprehensive Summary The strategy of removable glycosylation modification was used to overcome the low-efficiency problem encountered in the chemical synthesis of the mirror-image D-version of the immunoglobulin(Ig)-like domain of tropomyosin receptor kinase A(DlgCTrkA),a protein molecule needed for mirror-image screening of D-peptide ligands targeting this cell membrane receptor.It was found that O-linked-β-N-acetyl-D-glucosamine(O-GlcNAc)modification at^(D)Ser^(312),or^(D)Ser^(320)can significantly improve the efficiency of DlgCTrkA synthesis and folding,while O-GlcNAc modification at^(D)Ser^(330)showed barely any improvement.This study provides a new example demonstrating the power of the removable glycosylation modification strategy in the chemical synthesis and folding of difficult-to-obtain proteins.It also presents evidence that removable glycosylation modification at different sites would significantly affect the efficiency of protein folding promoted by this strategy.
基金This work was financially supported by the National Key Research and Development Program of China(2021YFA0909400)the National Natural Science Foundation of China(22105123,22305152)+3 种基金the Shanghai Rising-Star Program(23QA1408600),the Explorer Program of the Science and Technology Commission of Shanghai Municipality(21TS1400400)the Interdisciplinary Program of Shanghai Jiao Tong University(YG2021QN35),the Innovative Research Team of High-Level Local Universities in Shanghai(SHSMU-ZDCX20210900)the Foundation of National Infrastructures for Translational Medicine(Shanghai)(TMSK-2021-119)the Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support(20181704).
文摘Sugar moieties present on bacterial surface serve as pivotal regulators of bacterial activity.Precisely adjusting the abundance and distribution of surface sugar moieties can offer an important approach to manipulating bacterial behavior,but has been proven to be difficult.Herein,surface topological glycosylation is reported to mediate the interaction of bacteria with mucous layer.Alkynes functionalized by sugar moieties with different branching are synthesized through iterative Michael addition and amide condensation reactions.By a copper-catalyzed azide-alkyne cycloaddition,the resulting compounds with different branching structures can be attached onto bacterial surface that is modified with azido groups.As a proof-of-concept study,a set of topologically glycosylated probiotics(TGPs)is prepared using linear,two-branched,and tetra-branched compounds,respectively.The interaction between mucin and TGPs was studied and the results demonstrate that,compared to unmodified bacteria,TGPs exhibit an enhanced adhesive capacity to mucin,which increases with the branching numbers.Similar binding trend is observed in ex vivo colonic mucus adhesion experiments and bacteria glycosylated with tetra-branched compounds display the highest binding efficiency.This work proposes a chemical method to tune the abundance and distribution of sugar moieties on bacteria,providing unique significant insights into the manipulation of bacterial behavior through surface modification.
文摘利用转谷氨酰胺酶(transglutaminase,TGase)催化玉米醇溶蛋白与氨基葡萄糖盐酸盐(glucosamine hydrochloride,GAH)发生交联反应。通过SDS-聚丙烯酰胺凝胶电泳确认玉米醇溶蛋白与GAH发生交联反应。以玉米醇溶蛋白糖基化修饰产物中GAH导入量为指标,优化糖基化反应条件,并对玉米醇溶蛋白糖基化修饰样品的溶解性进行了表征。结果表明,最适的糖基化反应条件为底物质量浓度5 g/100 m L、TGase添加量50 U/g(以玉米醇溶蛋白计)、玉米醇溶蛋白中酰基供体与GAH中的酰基受体物质的量比1∶6、初始p H 8.0、反应温度44℃、反应时间7 h;此反应条件下,玉米醇溶蛋白中GAH的最大导入量为(11.34±0.21)mg/g(以玉米醇溶蛋白计)。与玉米醇溶蛋白相比,玉米醇溶蛋白交联样品与糖基化修饰样品的溶解性均得到提高,玉米醇溶蛋白糖基化修饰样品的溶解性最高。
