Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzy...Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzymes;and lymphocyte activation and proliferation. Cyclic ad-enosine diphosphate ribose(cADPR) is an endogenousCa2+ mobilizing nucleotide present in many cell typesand species, from plants to animals. cADPR is formedby ADP-ribosyl cyclases from nicotinamide adenine di-nucleotide. The main ADP-ribosyl cyclase in mammalsis CD38, a multi-functional enzyme and a type Ⅱ mem-brane protein. It has been shown that many extracel-lular stimuli can induce cADPR production that leadsto calcium release or influx, establishing cADPR as asecond messenger. cADPR has been linked to a widevariety of cellular processes, but the molecular mecha-nisms regarding cADPR signaling remain elusive. Theaim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advanc-es involving the mechanism and physiological functionsof cADPR-mediated Ca2+ mobilization.展开更多
The electrochemical behavior of the adenosine5diphosphate(ADP) was studied in 005 molL-1 MES buffer solution(pH 585) at mercury electrode. There are no reduction and oxidation waves for the adenosine5diphosphate in th...The electrochemical behavior of the adenosine5diphosphate(ADP) was studied in 005 molL-1 MES buffer solution(pH 585) at mercury electrode. There are no reduction and oxidation waves for the adenosine5diphosphate in the range of -04-14 V(vs. Ag/AgCl). In a mixture solution of Eu3+ and ADP(Eu3+ADP=14), a reduction peak is obtained at -078 V. Comparing with the cyclic voltammograms of Eu3+ ions under the same experimental conditions, it is found that the complex of Eu3+ADP can be produced in above solutions between Eu3+ion and ADP. The complex is strongly adsorbed at mercury electrode and has the following electrode reaction mechanism: Eu3++ADPEu3+ADP+e-Eu2+-ADP.展开更多
The development of colorectal cancer(CRC)can result from changes in a variety of cellular systems within the tumor microenvironment.Particularly,it is primarily associated with genomic instability that is the gradual ...The development of colorectal cancer(CRC)can result from changes in a variety of cellular systems within the tumor microenvironment.Particularly,it is primarily associated with genomic instability that is the gradual accumulation of genetic and epigenetic changes consisting of a characteristic set of mutations crucial for pathways in CRC progression.Based on this background,the potential to focus on poly[adenosine diphosphate(ADP)-ribose]polymerase(PARP)-1 and poly-ADP ribosylation(PARylation)as the main causes of malignant formation of CRC may be considered.One of the important functions of PARP-1 and PARylation is its deoxyribonucleic acid(DNA)repair function,which plays a pivotal role in the DNA damage response and prevention of DNA damage maintaining the redox homeostasis involved in the regulation of oxidation and superoxide.PARP-1 and PARylation can also alter epigenetic markers and chromatin structure involved in transcriptional regulation for the oncogenes or tumor suppressor genes by remodeling histone and chromatin enzymes.Given the high importance of these processes in CRC,it can be considered that PARP-1 and PARylation are at the forefront of the pathological changes required for CRC progression.Therefore,this review addresses the current molecular biological features for understanding the multifactorial function of PARP-1 and PARylation in CRC related to the aforementioned roles;furthermore,it presents a summary of recent approaches with PARP-1 inhibition in non-clinical and clinical studies targeting CRC.This understanding could help embrace the importance of targeting PARP-1 and PARylation in the treatment of CRC,which may present the potential to identify various research topics that can be challenged both nonclinically and clinically.展开更多
Turbidimetry and radioimmunoassay were used to study the effects of procainamide (PA ) onadenosine diphosphate (ADP)-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production invitro. PA 8. 5--544. 0 μ...Turbidimetry and radioimmunoassay were used to study the effects of procainamide (PA ) onadenosine diphosphate (ADP)-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production invitro. PA 8. 5--544. 0 μmol L-1 inhibited ADP-induced platelet aggregation and TXB2 production, and theinhibition rates were 26. 7% -- 66. 7 % and 21. 4 % -- 70. 1 %, respectively. There was positive correlation between PA concentration and its efficiency in inhibiting the platelet aggregation and TXB2 production, and alsobetween the inhibition rates of platelet aggregation and that of TXB2 production. The three linear equationsand main parameters were The results indicate that PA could significantly inhibit ADP--induced platelet aggregation and TXB2 production in rabbits.展开更多
Background Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to as...Background Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.Methods A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel （n=104） served as the Talcom （Taijia）group; others （n=101） received Plavix, the Plavix group, Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% （the primary endpoint） compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.Results Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a ＞50% decrease in adenosine phosphate-mediated platelet aggregation （rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P=0.028）. There was no significant difference in the eligible index between the Talcom and Plavix groups （47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P ＞0.05） based on a standard adenosine diphosphate-mediated platelet aggregation decrease of ＞50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events （2.5% vs. 2.9%, P=5.43）. No acute or subacute stent thrombosis events occurred.Conclusion An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.展开更多
Polar auxin transport,which depends on polarized subcellular distribution of AUXIN RESISTANT 1/LIKE AUX1（AUX1/LAX） influx carriers and PIN-FORMED（PIN） efflux carriers,mediates various processes of plant growth and...Polar auxin transport,which depends on polarized subcellular distribution of AUXIN RESISTANT 1/LIKE AUX1（AUX1/LAX） influx carriers and PIN-FORMED（PIN） efflux carriers,mediates various processes of plant growth and development.Endosomal recycling of PIN1 is mediated by an adenosine diphosphate（ADP）ribosylation factor（ARF）-GTPase exchange factor protein,GNOM.However,the mediation of auxin influx carrier recycling is poorly understood.Here,we report that overexpression of OsAGAP,an ARF-GTPase-activating protein in rice,stimulates vesicle transport from the plasma membrane to the Golgi apparatus in protoplasts and transgenic plants and induces the accumulation of early endosomes and AUX1.AUX1 endosomes could partially colocalize with FM4-64 labeled early endosome after actin disruption.Furthermore,OsAGAP is involved in actin cytoskeletal organization,and its overexpression tends to reduce the thickness and bundling of actin filaments.Fluorescence recovery after photobleaching analysis revealed exocytosis of the AUX1 recycling endosome was not affected in the OsAGAP overexpression cells,and was only slightly promoted when the actin filaments were completely disrupted by Lat B.Thus,we propose that AUX1 accumulation in the OsAGAP overexpression and actin disrupted cells may be due to the fact that endocytosis of the auxin influx carrier AUX1 early endosome was greatly promoted by actin cytoskeleton disruption.展开更多
Background： Acute lung injury （ALI） is a common complication of sepsis that is associated with high mortality, lntracellular Ca^2＋ overload plays an important role in the pathophysiology of sepsis-induced ALl, and...Background： Acute lung injury （ALI） is a common complication of sepsis that is associated with high mortality, lntracellular Ca^2＋ overload plays an important role in the pathophysiology of sepsis-induced ALl, and cyclic adenosine diphosphate ribose （cADPR） is an important regulator of intracellular Ca^2＋ mobilization. The cluster of differentiation 38 （CD38）/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALl is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALl and whether blocking cADPR-mediated calcium overload attenuates ALl. Methods： Septic rat models were established by cecal ligation and puncture （CLP）. Rats were divided into the sham group, the CLP group, and the CLP＋ 8-bromo-cyclic adenosine diphosphate ribose （8-Br-cADPR） group. Nicotinamide adenine dinucleotide （NAD＋）, cADPR, CD38, and intracellular Ca^2＋ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor （TNF）-a, malondialdehyde （MDA） levels, and superoxide dismutase （SOD） activities were measured. Results： NAD＋, cADPR, CD38, and intracellular Ca-＋ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca^2＋ levels （P = 0.007）, attenuated lung histological injury （P = 0.023）, reduced TNF-a and MDA levels （P 〈 0.001 and P = 0.002, respectively） and recovered SOD activity （P = 0.031） in the lungs of septic rats. Conclusions： The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALl.展开更多
In flowering plants, male gametes are delivered to female gametophytes by pollen tubes. Although it is important for sexual plant reproduction, little is known about the genetic mechanism that controls pollen germinat...In flowering plants, male gametes are delivered to female gametophytes by pollen tubes. Although it is important for sexual plant reproduction, little is known about the genetic mechanism that controls pollen germination and pollen tube growth. Here we report the identification and characterization of two novel mutants, gnom-like 2-1 （gnl2-1） and gn12-2 in Arabidopsis thaliana, in which the pollen grains failed to germinate in vitro and in vivo. GNL2 encodes a protein homologous to the adenosine diphosphate-ribosylation factor-guanine nucleotide exchange factors, GNOM and GNL1 that are involved in endosomal recycling and endoplasmic reticulum-Golgi vesicular trafficking. It was prolifically expressed in pollen grains and pollen tubes. The results of the present study suggest that GNL2 plays an important role in pollen germination.展开更多
基金Supported by Research Grant Council grants,No.782709M,No.785911M,No.769912M and No.785213M
文摘Mobilization of intracellular Ca2+ stores is involved inmany diverse cell functions, including: cell proliferation;differentiation; fertilization; muscle contraction; secre-tion of neurotransmitters, hormones and enzymes;and lymphocyte activation and proliferation. Cyclic ad-enosine diphosphate ribose(cADPR) is an endogenousCa2+ mobilizing nucleotide present in many cell typesand species, from plants to animals. cADPR is formedby ADP-ribosyl cyclases from nicotinamide adenine di-nucleotide. The main ADP-ribosyl cyclase in mammalsis CD38, a multi-functional enzyme and a type Ⅱ mem-brane protein. It has been shown that many extracel-lular stimuli can induce cADPR production that leadsto calcium release or influx, establishing cADPR as asecond messenger. cADPR has been linked to a widevariety of cellular processes, but the molecular mecha-nisms regarding cADPR signaling remain elusive. Theaim of this review is to summarize the CD38/cADPR/Ca2+ signaling pathway, focusing on the recent advanc-es involving the mechanism and physiological functionsof cADPR-mediated Ca2+ mobilization.
文摘The electrochemical behavior of the adenosine5diphosphate(ADP) was studied in 005 molL-1 MES buffer solution(pH 585) at mercury electrode. There are no reduction and oxidation waves for the adenosine5diphosphate in the range of -04-14 V(vs. Ag/AgCl). In a mixture solution of Eu3+ and ADP(Eu3+ADP=14), a reduction peak is obtained at -078 V. Comparing with the cyclic voltammograms of Eu3+ ions under the same experimental conditions, it is found that the complex of Eu3+ADP can be produced in above solutions between Eu3+ion and ADP. The complex is strongly adsorbed at mercury electrode and has the following electrode reaction mechanism: Eu3++ADPEu3+ADP+e-Eu2+-ADP.
文摘The development of colorectal cancer(CRC)can result from changes in a variety of cellular systems within the tumor microenvironment.Particularly,it is primarily associated with genomic instability that is the gradual accumulation of genetic and epigenetic changes consisting of a characteristic set of mutations crucial for pathways in CRC progression.Based on this background,the potential to focus on poly[adenosine diphosphate(ADP)-ribose]polymerase(PARP)-1 and poly-ADP ribosylation(PARylation)as the main causes of malignant formation of CRC may be considered.One of the important functions of PARP-1 and PARylation is its deoxyribonucleic acid(DNA)repair function,which plays a pivotal role in the DNA damage response and prevention of DNA damage maintaining the redox homeostasis involved in the regulation of oxidation and superoxide.PARP-1 and PARylation can also alter epigenetic markers and chromatin structure involved in transcriptional regulation for the oncogenes or tumor suppressor genes by remodeling histone and chromatin enzymes.Given the high importance of these processes in CRC,it can be considered that PARP-1 and PARylation are at the forefront of the pathological changes required for CRC progression.Therefore,this review addresses the current molecular biological features for understanding the multifactorial function of PARP-1 and PARylation in CRC related to the aforementioned roles;furthermore,it presents a summary of recent approaches with PARP-1 inhibition in non-clinical and clinical studies targeting CRC.This understanding could help embrace the importance of targeting PARP-1 and PARylation in the treatment of CRC,which may present the potential to identify various research topics that can be challenged both nonclinically and clinically.
文摘Turbidimetry and radioimmunoassay were used to study the effects of procainamide (PA ) onadenosine diphosphate (ADP)-induced rabbit platelet aggregation and thromboxane B2 (TXB2) production invitro. PA 8. 5--544. 0 μmol L-1 inhibited ADP-induced platelet aggregation and TXB2 production, and theinhibition rates were 26. 7% -- 66. 7 % and 21. 4 % -- 70. 1 %, respectively. There was positive correlation between PA concentration and its efficiency in inhibiting the platelet aggregation and TXB2 production, and alsobetween the inhibition rates of platelet aggregation and that of TXB2 production. The three linear equationsand main parameters were The results indicate that PA could significantly inhibit ADP--induced platelet aggregation and TXB2 production in rabbits.
文摘Background Adenosine phosphate-mediated platelet aggregation is a prognostic factor for major adverse cardiac events in patients who have undergone selective percutaneous coronary interventions. This study aimed to assess whether an adjusted loading dose of clopidogrel could more effectively inhibit platelet aggregation in patients undergoing selected percutaneous coronary intervention.Methods A total of 205 patients undergoing selected percutaneous coronary intervention were enrolled in this multicenter, prospective, randomized study. Patients receiving domestic clopidogrel （n=104） served as the Talcom （Taijia）group; others （n=101） received Plavix, the Plavix group, Patients received up to 3 additional 300-mg loading doses of clopidogrel to decrease the adenosine phosphate-mediated platelet aggregation index by more than 50% （the primary endpoint） compared with the baseline. The secondary endpoint was major adverse cardiovascular events at 12 months.Results Compared with the rational loading dosage, the tailored loading dosage better inhibited platelet aggregation based on a ＞50% decrease in adenosine phosphate-mediated platelet aggregation （rational loading dosage vs. tailored loading dosage, 48% vs. 73%, P=0.028）. There was no significant difference in the eligible index between the Talcom and Plavix groups （47% vs. 49% at 300 mg; 62% vs. 59% at 600 mg; 74% vs. 72% at 900 mg; P ＞0.05） based on a standard adenosine diphosphate-mediated platelet aggregation decrease of ＞50%. After 12 months of follow-up, there were no significant differences in major adverse cardiac events （2.5% vs. 2.9%, P=5.43）. No acute or subacute stent thrombosis events occurred.Conclusion An adjusted loading dose of clopidogrel could have significant effects on antiplatelet aggregation compared with a rational dose, decreasing 1-year major adverse cardiac events in patients undergoing percutaneous coronary interventions based on adenosine phosphate-mediated platelet aggregation with no increase in bleeding.
基金supported by the Innovative Program of the Chinese Academy of Sciences (KSCX2-YW-N-041)the National Natural Science Foundation of China(30670197)
文摘Polar auxin transport,which depends on polarized subcellular distribution of AUXIN RESISTANT 1/LIKE AUX1（AUX1/LAX） influx carriers and PIN-FORMED（PIN） efflux carriers,mediates various processes of plant growth and development.Endosomal recycling of PIN1 is mediated by an adenosine diphosphate（ADP）ribosylation factor（ARF）-GTPase exchange factor protein,GNOM.However,the mediation of auxin influx carrier recycling is poorly understood.Here,we report that overexpression of OsAGAP,an ARF-GTPase-activating protein in rice,stimulates vesicle transport from the plasma membrane to the Golgi apparatus in protoplasts and transgenic plants and induces the accumulation of early endosomes and AUX1.AUX1 endosomes could partially colocalize with FM4-64 labeled early endosome after actin disruption.Furthermore,OsAGAP is involved in actin cytoskeletal organization,and its overexpression tends to reduce the thickness and bundling of actin filaments.Fluorescence recovery after photobleaching analysis revealed exocytosis of the AUX1 recycling endosome was not affected in the OsAGAP overexpression cells,and was only slightly promoted when the actin filaments were completely disrupted by Lat B.Thus,we propose that AUX1 accumulation in the OsAGAP overexpression and actin disrupted cells may be due to the fact that endocytosis of the auxin influx carrier AUX1 early endosome was greatly promoted by actin cytoskeleton disruption.
文摘Background： Acute lung injury （ALI） is a common complication of sepsis that is associated with high mortality, lntracellular Ca^2＋ overload plays an important role in the pathophysiology of sepsis-induced ALl, and cyclic adenosine diphosphate ribose （cADPR） is an important regulator of intracellular Ca^2＋ mobilization. The cluster of differentiation 38 （CD38）/cADPR pathway has been found to play roles in multiple inflammatory processes but its role in sepsis-induced ALl is still unknown. This study aimed to investigate whether the CD38/cADPR signaling pathway is activated in sepsis-induced ALl and whether blocking cADPR-mediated calcium overload attenuates ALl. Methods： Septic rat models were established by cecal ligation and puncture （CLP）. Rats were divided into the sham group, the CLP group, and the CLP＋ 8-bromo-cyclic adenosine diphosphate ribose （8-Br-cADPR） group. Nicotinamide adenine dinucleotide （NAD＋）, cADPR, CD38, and intracellular Ca^2＋ levels in the lung tissues were measured at 6, 12, 24, and 48 h after CLP surgery. Lung histologic injury, tumor necrosis factor （TNF）-a, malondialdehyde （MDA） levels, and superoxide dismutase （SOD） activities were measured. Results： NAD＋, cADPR, CD38, and intracellular Ca-＋ levels in the lungs of septic rats increased significantly at 24 h after CLP surgery. Treatment with 8-Br-cADPR, a specific inhibitor of cADPR, significantly reduced intracellular Ca^2＋ levels （P = 0.007）, attenuated lung histological injury （P = 0.023）, reduced TNF-a and MDA levels （P 〈 0.001 and P = 0.002, respectively） and recovered SOD activity （P = 0.031） in the lungs of septic rats. Conclusions： The CD38/cADPR pathway is activated in the lungs of septic rats, and blocking cADPR-mediated calcium overload with 8-Br-cADPR protects against sepsis-induced ALl.
基金Supported by the National Natural Science Foundation of China (30530060)the State Key Basic Research and Development Plan of China(2007CB108700)the Ministry of Education (111 project numberedB06003)
文摘In flowering plants, male gametes are delivered to female gametophytes by pollen tubes. Although it is important for sexual plant reproduction, little is known about the genetic mechanism that controls pollen germination and pollen tube growth. Here we report the identification and characterization of two novel mutants, gnom-like 2-1 （gnl2-1） and gn12-2 in Arabidopsis thaliana, in which the pollen grains failed to germinate in vitro and in vivo. GNL2 encodes a protein homologous to the adenosine diphosphate-ribosylation factor-guanine nucleotide exchange factors, GNOM and GNL1 that are involved in endosomal recycling and endoplasmic reticulum-Golgi vesicular trafficking. It was prolifically expressed in pollen grains and pollen tubes. The results of the present study suggest that GNL2 plays an important role in pollen germination.
