Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^...Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.展开更多
Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in viv...Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.展开更多
Cement pastes containing 0%, 15%, 25% and 35% fly ash were prepared. After being cured for 90 days, all fly ash blended cement pastes were crushed and ground into powders with a particle size less than 80 μm and then...Cement pastes containing 0%, 15%, 25% and 35% fly ash were prepared. After being cured for 90 days, all fly ash blended cement pastes were crushed and ground into powders with a particle size less than 80 μm and then the powders were immersed in alkali solutions. Adsorption characteristics of K^+ and Na^+ ions in the pastes were investigated. Meawhile, the desorption characteristics of the adsorbed alklai ions and the inherent K^+ and Na^+ ions in the pastes were also investigated. Results showed that the contents of K^+ and Na^+ ions adsorbed by the pastes increased with increasing the substitution levels of fly ash and/or the concentrations of alkali solutions. Each paste was characterized by having the same adsorption capacity for K^+ or Na^+ that was essentially independent of alkali concentration. Adsorption mechanism of K^+ and Na^+ ions by the pastes is believed to be an effect of charge compensation of the C-S-H gel. Adsorption-desorption of the adsorbed K^+ and Na^+ ions in the pastes is reversible. The inherent K^+ and Na^+ ions in the pastes entered rapidly into the de-ionized water during the first 120 minutes, and then they were released at a relatively slow rate. A steady-state alkali partition was reached at about 720 minutes. Some K^+ and Na^+ ions which were originally "bound" by the hydration products were considered to be released into de-ionized water. Leaching tests showed that there was no significant effect of fly ash on the retaining of available alkalis in the pastes. A part of the released alkali ions exists in the pore solutions and the other part may be physically adsorbed by the hydration products.展开更多
基金supported by the National Natural Science Foundation of China,No.82173800 (to JB)Shenzhen Science and Technology Program,No.KQTD20200820113040070 (to JB)。
文摘Na^(+)/K^(+)-ATPase is a transmembrane protein that has important roles in the maintenance of electrochemical gradients across cell membranes by transporting three Na^(+)out of and two K^(+)into cells.Additionally,Na^(+)/K^(+)-ATPase participates in Ca^(2+)-signaling transduction and neurotransmitter release by coordinating the ion concentration gradient across the cell membrane.Na^(+)/K^(+)-ATPase works synergistically with multiple ion channels in the cell membrane to form a dynamic network of ion homeostatic regulation and affects cellular communication by regulating chemical signals and the ion balance among different types of cells.Therefo re,it is not surprising that Na^(+)/K^(+)-ATPase dysfunction has emerged as a risk factor for a variety of neurological diseases.However,published studies have so far only elucidated the important roles of Na^(+)/K^(+)-ATPase dysfunction in disease development,and we are lacking detailed mechanisms to clarify how Na^(+)/K^(+)-ATPase affects cell function.Our recent studies revealed that membrane loss of Na^(+)/K^(+)-ATPase is a key mechanism in many neurological disorders,particularly stroke and Parkinson's disease.Stabilization of plasma membrane Na^(+)/K^(+)-ATPase with an antibody is a novel strategy to treat these diseases.For this reason,Na^(+)/K^(+)-ATPase acts not only as a simple ion pump but also as a sensor/regulator or cytoprotective protein,participating in signal transduction such as neuronal autophagy and apoptosis,and glial cell migration.Thus,the present review attempts to summarize the novel biological functions of Na^(+)/K^(+)-ATPase and Na^(+)/K^(+)-ATPase-related pathogenesis.The potential for novel strategies to treat Na^(+)/K^(+)-ATPase-related brain diseases will also be discussed.
基金supported by the Natural Science Foundation of Fujian Province,No.2020J02027the National Natural Science Foundation of China,No.31970461the Foundation of NHC Key Laboratory of Technical Evaluation of Fertility Regulation for Non-human Primate,Fujian Maternity and Child Health Hospital,No.2022-NHP-05(all to WC).
文摘Certain amino acids changes in the human Na^(+)/K^(+)-ATPase pump,ATPase Na^(+)/K^(+)transporting subunit alpha 1(ATP1A1),cause Charcot-Marie-Tooth disease type 2(CMT2)disease and refractory seizures.To develop in vivo models to study the role of Na^(+)/K^(+)-ATPase in these diseases,we modified the Drosophila gene homolog,Atpα,to mimic the human ATP1A1 gene mutations that cause CMT2.Mutations located within the helical linker region of human ATP1A1(I592T,A597T,P600T,and D601F)were simultaneously introduced into endogenous Drosophila Atpαby CRISPR/Cas9-mediated genome editing,generating the Atpα^(TTTF)model.In addition,the same strategy was used to generate the corresponding single point mutations in flies(Atpα^(I571T),Atpα^(A576T),Atpα^(P579T),and Atpα^(D580F)).Moreover,a deletion mutation(Atpα^(mut))that causes premature termination of translation was generated as a positive control.Of these alleles,we found two that could be maintained as homozygotes(Atpα^(I571T)and Atpα^(P579T)).Three alleles(Atpα^(A576T),Atpα^(P579)and Atpα^(D580F))can form heterozygotes with the Atpαmut allele.We found that the Atpαallele carrying these CMT2-associated mutations showed differential phenotypes in Drosophila.Flies heterozygous for Atpα^(TTTF)mutations have motor performance defects,a reduced lifespan,seizures,and an abnormal neuronal morphology.These Drosophila models will provide a new platform for studying the function and regulation of the sodium-potassium pump.
基金Funded by the National Natural Science Foundation of China(No.51578004)the Program for Changjiang Scholars and Innovative Research Team in University(PCSIRT)(No.IRT1146)the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)。
文摘Cement pastes containing 0%, 15%, 25% and 35% fly ash were prepared. After being cured for 90 days, all fly ash blended cement pastes were crushed and ground into powders with a particle size less than 80 μm and then the powders were immersed in alkali solutions. Adsorption characteristics of K^+ and Na^+ ions in the pastes were investigated. Meawhile, the desorption characteristics of the adsorbed alklai ions and the inherent K^+ and Na^+ ions in the pastes were also investigated. Results showed that the contents of K^+ and Na^+ ions adsorbed by the pastes increased with increasing the substitution levels of fly ash and/or the concentrations of alkali solutions. Each paste was characterized by having the same adsorption capacity for K^+ or Na^+ that was essentially independent of alkali concentration. Adsorption mechanism of K^+ and Na^+ ions by the pastes is believed to be an effect of charge compensation of the C-S-H gel. Adsorption-desorption of the adsorbed K^+ and Na^+ ions in the pastes is reversible. The inherent K^+ and Na^+ ions in the pastes entered rapidly into the de-ionized water during the first 120 minutes, and then they were released at a relatively slow rate. A steady-state alkali partition was reached at about 720 minutes. Some K^+ and Na^+ ions which were originally "bound" by the hydration products were considered to be released into de-ionized water. Leaching tests showed that there was no significant effect of fly ash on the retaining of available alkalis in the pastes. A part of the released alkali ions exists in the pore solutions and the other part may be physically adsorbed by the hydration products.