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
Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucia...Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.展开更多
Acidic digestion is an important digestive process of marine fish.In fish stomach,two enzymes are involved in the secretion of hydrochloric acid(HCl)and proteomic digestion:H^(+)/K^(+)-ATPase and pepsinogen.However,th...Acidic digestion is an important digestive process of marine fish.In fish stomach,two enzymes are involved in the secretion of hydrochloric acid(HCl)and proteomic digestion:H^(+)/K^(+)-ATPase and pepsinogen.However,the starting of digestive function in fish is still unclear.To reveal the details of acidic digestion of turbot Scophthalmus maximus in early development,a 40 day of turbot larvae culture was conducted.The H^(+)/K^(+)-ATPase gene from the turbot S.maximus(smH^(+)/K^(+)-ATPase)was identified and characterized.Based on our previous discription on pepsinogen of turbot S.maximus,we combined pepsinogen and H^(+)/K^(+)-ATPase and analyzed the mechanism of acidic digestion in turbot.Results show that the spatial and temporal expression profiles of H^(+)/K^(+)-ATPase agreed with pepsinogen A and C in turbot,indicating a synergetic action between H^(+)/K^(+)-ATPase and pepsinogen during the acidic digestion process.In addition,the turbot juveniles showed a faster growth after the expressions of H^(+)/K^(+)-ATPase gene and pepsinogen gene,demonstrating that pepsin had a higher digestive efficiency,for which a compound diet should be provided to the fish from Day 22 onward.This study provided a reference for biology research and aquaculture of turbot and other marine fishes.展开更多
Plants are sources of medicinal compounds,and they play a crucial role in human health maintenance.Abrus precatorius is one of the important medicinal plants that have been alleged for their medicinal properties.This ...Plants are sources of medicinal compounds,and they play a crucial role in human health maintenance.Abrus precatorius is one of the important medicinal plants that have been alleged for their medicinal properties.This research unraveled the pharmacological effect of ethanolic extract of Abrus precatorius on lipid peroxidation,liver parameters,and Na^(+)/K^(+)-ATPase activity in HgCl_(2) treated wistar rats.Twenty-four(24)albino wistar rats weighing between 150-200 g were distributed into four groups of 6 animals each.Group A(control)received normal saline(0.9% NaCl),group B received 400 mg/kg of the extract only,group C received 4 mg/kg HgCl_(2) only,and group D received 400 mg/kg of extract+4 mg/kg of HgCl_(2).The treatment lasted for two weeks,and the animals were sacrificed on the 15th day.The blood,brains and livers were collected and used for assay of lipid peroxidation,liver function,and sodium pump activity.The results of liver function test revealed an elevated(P<0.05)level of serum aspartate transaminase,alanine transaminase,alkaline phosphatase,and total bilirubin in the group that received HgCl_(2) only(group C)when compared with the normal control(group A)that received normal saline only.However,the administration of extract in group D led to a marked(P<0.05)reduction in the activities of these enzymes and the level of total bilirubin when compared to the negative control(group C).On the contrary,HgCl_(2) caused a significant(P<0.05)reduction in serum total protein and albumin levels,but the extract reversed the effect of HgCl_(2) by elevating their concentrations.Nonetheless,the effect elicited by this extract is comparable to group A which received normal saline.Moreso,the result of lipid peroxidation revealed that HgCl_(2) treatment caused a marked(P<0.05)increase in the formation of lipid peroxidation adducts in both liver and brain homogenates in group C.On the contrary,administration of Abrus precatorius extract profoundly(P<0.05)inhibited HgCl_(2)-induced lipid peroxidation in group D.In addition,HgCl_(2) inhibited the activity of cerebral Na^(+)/K^(+)-ATPase,but the extract restored normalcy by increasing the activity of the enzyme in group D.Consequently,the results obtained justify the traditional use of Abrus precatorius and suggest that Abrus precatorius leaves may be used for management of liver diseases,oxidative stress-linked diseases and some neurodegenerative ailments.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 National Natural Science Foundation of China(Youth Program),No.81901282(to XC)the National Natural Science Foundation of China,Nos.81401416(to PX),81870992(to PX),81870856(to XC and MZ)+3 种基金Guangdong Basic and Applied Basic Research Foundation the Science Foundation,No.2019A1515011189(to XC)Central Government Guiding Local Science and Technology Development Projects,No.ZYYD2022C17(to PX)Key Project of Guangzhou Health Commission,No.2019-ZD-09(to PX)Science and Technology Planning Project of Guangzhou,Nos.202102020029(to XC),202102010010(to PX)。
文摘Mitochondrial dysfunction is a significant pathological alte ration that occurs in Parkinson's disease(PD),and the Thr61lle(T61I)mutation in coiled-coil helix coiled-coil helix domain containing 2(CHCHD2),a crucial mitochondrial protein,has been reported to cause Parkinson's disease.FIFO-ATPase participates in the synthesis of cellular adenosine triphosphate(ATP)and plays a central role in mitochondrial energy metabolism.However,the specific roles of wild-type(WT)CHCHD2 and T611-mutant CHCHD2 in regulating F1FO-ATPase activity in Parkinson's disease,as well as whether CHCHD2 or CHCHD2 T61I affects mitochondrial function through regulating F1FO-ATPase activity,remain unclea r.Therefore,in this study,we expressed WT CHCHD2 and T61l-mutant CHCHD2 in an MPP^(+)-induced SH-SY5Y cell model of PD.We found that CHCHD2 protected mitochondria from developing MPP^(+)-induced dysfunction.Under normal conditions,ove rexpression of WT CHCHD2 promoted F1FO-ATPase assembly,while T61I-mutant CHCHD2 appeared to have lost the ability to regulate F1FO-ATPase assembly.In addition,mass spectrometry and immunoprecipitation showed that there was an interaction between CHCHD2 and F1FO-ATPase.Three weeks after transfection with AAV-CHCHD2 T61I,we intraperitoneally injected 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine into mice to establish an animal model of chronic Parkinson's disease and found that exogenous expression of the mutant protein worsened the behavioral deficits and dopaminergic neurodegeneration seen in this model.These findings suggest that WT CHCHD2 can alleviate mitochondrial dysfunction in PD by maintaining F1F0-ATPase structure and function.
基金Supported by the National Key Research and Development Program(No.2018YFD0901204)the Key Special Project for Introduced Talents Team of Southern Marine Science and Engineering Guangdong Laboratory(Guangzhou)(No.GML2019ZD0402)+3 种基金the Major Agricultural Application Technology Innovation Project of Shandong Province(No.SD2019YY011)the Qingdao National Laboratory for Marine Science and Technology(No.2018SDKJ0502-2)the China Agriculture Research System(No.CARS-47),the Major Science and Technology for Scientific and Technological Innovation Projects(Shandong)(No.2019JZZY020710)the STS Project(Nos.KFZD-SW-106,ZSSD-019,2017T3017,2019T3022)。
文摘Acidic digestion is an important digestive process of marine fish.In fish stomach,two enzymes are involved in the secretion of hydrochloric acid(HCl)and proteomic digestion:H^(+)/K^(+)-ATPase and pepsinogen.However,the starting of digestive function in fish is still unclear.To reveal the details of acidic digestion of turbot Scophthalmus maximus in early development,a 40 day of turbot larvae culture was conducted.The H^(+)/K^(+)-ATPase gene from the turbot S.maximus(smH^(+)/K^(+)-ATPase)was identified and characterized.Based on our previous discription on pepsinogen of turbot S.maximus,we combined pepsinogen and H^(+)/K^(+)-ATPase and analyzed the mechanism of acidic digestion in turbot.Results show that the spatial and temporal expression profiles of H^(+)/K^(+)-ATPase agreed with pepsinogen A and C in turbot,indicating a synergetic action between H^(+)/K^(+)-ATPase and pepsinogen during the acidic digestion process.In addition,the turbot juveniles showed a faster growth after the expressions of H^(+)/K^(+)-ATPase gene and pepsinogen gene,demonstrating that pepsin had a higher digestive efficiency,for which a compound diet should be provided to the fish from Day 22 onward.This study provided a reference for biology research and aquaculture of turbot and other marine fishes.
文摘Plants are sources of medicinal compounds,and they play a crucial role in human health maintenance.Abrus precatorius is one of the important medicinal plants that have been alleged for their medicinal properties.This research unraveled the pharmacological effect of ethanolic extract of Abrus precatorius on lipid peroxidation,liver parameters,and Na^(+)/K^(+)-ATPase activity in HgCl_(2) treated wistar rats.Twenty-four(24)albino wistar rats weighing between 150-200 g were distributed into four groups of 6 animals each.Group A(control)received normal saline(0.9% NaCl),group B received 400 mg/kg of the extract only,group C received 4 mg/kg HgCl_(2) only,and group D received 400 mg/kg of extract+4 mg/kg of HgCl_(2).The treatment lasted for two weeks,and the animals were sacrificed on the 15th day.The blood,brains and livers were collected and used for assay of lipid peroxidation,liver function,and sodium pump activity.The results of liver function test revealed an elevated(P<0.05)level of serum aspartate transaminase,alanine transaminase,alkaline phosphatase,and total bilirubin in the group that received HgCl_(2) only(group C)when compared with the normal control(group A)that received normal saline only.However,the administration of extract in group D led to a marked(P<0.05)reduction in the activities of these enzymes and the level of total bilirubin when compared to the negative control(group C).On the contrary,HgCl_(2) caused a significant(P<0.05)reduction in serum total protein and albumin levels,but the extract reversed the effect of HgCl_(2) by elevating their concentrations.Nonetheless,the effect elicited by this extract is comparable to group A which received normal saline.Moreso,the result of lipid peroxidation revealed that HgCl_(2) treatment caused a marked(P<0.05)increase in the formation of lipid peroxidation adducts in both liver and brain homogenates in group C.On the contrary,administration of Abrus precatorius extract profoundly(P<0.05)inhibited HgCl_(2)-induced lipid peroxidation in group D.In addition,HgCl_(2) inhibited the activity of cerebral Na^(+)/K^(+)-ATPase,but the extract restored normalcy by increasing the activity of the enzyme in group D.Consequently,the results obtained justify the traditional use of Abrus precatorius and suggest that Abrus precatorius leaves may be used for management of liver diseases,oxidative stress-linked diseases and some neurodegenerative ailments.
