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
The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role o...The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.展开更多
BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the r...BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the radiation-induced changes in the expression of K_(ATP)channel subunits in the mouse liver to understand the potential role of K_(ATP)channels in radiation injury.METHODS Adult C57BL/6 mice were randomly exposed toγ-rays at 0 Gy(control,n=2),0.2 Gy(n=6),1 Gy(n=6),or 5 Gy(n=6).The livers were removed 3 and 24 h after radiation exposure.Hematoxylin and eosin staining was used for morphological observation;immunohistochemical staining was applied to determine the expression of K_(ATP)channel subunits in the liver tissue.RESULTS Compared with the control group,the livers exposed to 0.2 Gyγ-ray showed an initial increase in the expression of Kir6.1 at 3 h,followed by recovery at 24 h after exposure.Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h.However,the expression of Kir6.2,SUR1,or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses.CONCLUSION The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses,suggesting a potential role for them in radiation-induced liver injury.展开更多
TWIK-related acid-sensitive K+(TASK) channels give rise to leak K+ currents which influence the resting membrane potential and input resistance. The wide expression of TASK1 and TASK3 channels in the central nervous s...TWIK-related acid-sensitive K+(TASK) channels give rise to leak K+ currents which influence the resting membrane potential and input resistance. The wide expression of TASK1 and TASK3 channels in the central nervous system suggests that these channels are critically involved in neurological disorders. It has become apparent in the past decade that TASK channels play critical roles for the development of various neurological disorders. In this review, I describe evidence for their roles in ischemia, epilepsy, learning/memory/cognition and apoptosis.展开更多
The shear stress distribution in circular channels was modeled in this study using gene expression programming(GEP). 173 sets of reliable data were collected under four flow conditions for use in the training and test...The shear stress distribution in circular channels was modeled in this study using gene expression programming(GEP). 173 sets of reliable data were collected under four flow conditions for use in the training and testing stages. The effect of input variables on GEP modeling was studied and 15 different GEP models with individual, binary, ternary, and quaternary input combinations were investigated. The sensitivity analysis results demonstrate that dimensionless parameter y/P, where y is the transverse coordinate, and P is the wetted perimeter, is the most influential parameter with regard to the shear stress distribution in circular channels. GEP model 10, with the parameter y/P and Reynolds number(Re) as inputs, outperformed the other GEP models, with a coefficient of determination of 0.7814 for the testing data set. An equation was derived from the best GEP model and its results were compared with an artificial neural network(ANN) model and an equation based on the Shannon entropy proposed by other researchers. The GEP model, with an average RMSE of 0.0301, exhibits superior performance over the Shannon entropy-based equation, with an average RMSE of 0.1049, and the ANN model, with an average RMSE of 0.2815 for all flow depths.展开更多
The Cl^- homeostasis was known as the major mechanism of soybean to achieve NaCl tolerance, but studies on the role of chloride channel under abiotic stress were relatively few. We cloned a putative CLC-type chloride ...The Cl^- homeostasis was known as the major mechanism of soybean to achieve NaCl tolerance, but studies on the role of chloride channel under abiotic stress were relatively few. We cloned a putative CLC-type chloride channel gene GmCLCnt from soybean via RACE and it was predicted to encode a protein of 783 amino acids with 9 possible transmembrane domains and 2 tandem CBS domains. Real-time RT-PCR analysis showed that the GmCLCnt gene was expressed in all tissues of soybean but enriched in leaves and its expression was induced by NaCl, polyethylene glycol （PEG）, coldness and ABA treatments. The Arabidopsis seedlings overexpressing GmCLCnt were more tolerant to higher concentration of NaCl than those of wild type. The results suggested that the GmCLCnt may be a CLC-type chloride channel and play an important role in salt tolerance.展开更多
The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage,...The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations （0, 25, 50, 100, 200 μg/mL） of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^＋ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase （LDH） and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^＋ current. Exposure to quartz particles increased the outward delayed K^＋ current but it had no effect on inward rectifier K^＋ current in AMs. Neither of the two K^＋ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH （P〈0.05）. MTT studies, however, showed that only quartz particles reduced viability of AMs （P〈0.05）. It is concluded that quartz parti- cles can activate the outward delayed K^＋ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^＋ channels do not contribute to the membrane damage of AMs.展开更多
BACKGROUND ATP-sensitive K^+(KATP)channels were originally found in cardiac myocytes by Noma in 1983.KATP channels were formed by potassium ion-passing poreforming subunits(Kir6.1,Kir6.2)and regulatory subunits SUR1,S...BACKGROUND ATP-sensitive K^+(KATP)channels were originally found in cardiac myocytes by Noma in 1983.KATP channels were formed by potassium ion-passing poreforming subunits(Kir6.1,Kir6.2)and regulatory subunits SUR1,SU2A and SUR2B.A number of cells and tissues have been revealed to contain these channels including hepatocytes,but detailed localization of these subunits in different types of liver cells was still uncertain.AIM To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver.METHODS Rabbit anti-rat SUR1 peptide antibody was raised and purified by antigen immunoaffinity column chromatography.Four of Sprague-Dawley rats were used for liver protein extraction for immunoblot analysis,seven of them were used for immunohistochemistry both for the ABC method and immunofluorescence staining.Four of Wistar rats were used for the isolation of hepatic stellate cells(HSCs)and Kupffer cells for both primary culture and immunocytochemistry.RESULTS Immunoblot analysis showed that the five kinds of KATP channel subunits,i.e.Kir6.1,Kir6.2,SUR1,SUR2A,and SUR2B,were detected in liver.Immunohistochemical staining showed that Kir6.1 and Kir6.2 were weakly to moderately expressed in parenchymal cells and sinusoidal lining cells,while SUR1,SUR2A,and SUR2B were mainly localized to sinusoidal lining cells,such as HSCs,Kupffer cells,and sinusoidal endothelial cells.Immunoreactivity for SUR2A and SUR2B was expressed in the hepatocyte membrane.Double immunofluorescence staining further showed that the pore-forming subunits Kir6.1 and/or Kir6.2 colocalized with GFAP in rat liver sections and primary cultured HSCs.These KATP channel subunits also colocalized with CD68 in liver sections and primary cultured Kupffer cells.The SUR subunits colocalized with GFAP in liver sections and colocalized with CD68 both in liver sections and primary cultured Kupffer cells.In addition,five KATP channel subunits colocalized with SE-1 in sinusoidal endothelial cells.CONCLUSION Observations from the present study indicated that KATP channel subunits expressed in rat liver and the diversity of KATP channel subunit composition might form different types of KATP channels.This is applicable to hepatocytes,HSCs,various types of Kupffer cells and sinusoidal endothelial cells.展开更多
The epithelial Na+ channel(ENa C) consists of α,β,γsubunits.Its expression and function are regulated by aldosterone at multiple levels including transcription.ENa C plays a key role in Na+ homeostasis and blood pr...The epithelial Na+ channel(ENa C) consists of α,β,γsubunits.Its expression and function are regulated by aldosterone at multiple levels including transcription.ENa C plays a key role in Na+ homeostasis and blood pressure.Mutations in ENa C subunit genes result in hypertension or hypotension,depending on the nature of the mutations.Transcription of αENa C is considered as the rate-limiting step in the formation of functional ENa C.As an aldosterone target gene,αENa C is activated upon aldosterone-mineralocorticoid receptor binding to the cis-elements in the αENa C promoter,which is packed into chromatin.However,how aldosterone alters chromatin structure to induce changes in transcription is poorly understood.Studies by others and us suggest that Dot1a-Af9 complex represses αENa C by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENa C promoter.Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1 a and Af9 and by inducing Sgk1,which,in turn,phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction.MR attenuates Dot1aAf9 effect by competing with Dot1 a for binding Af9.Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1 a nuclear export.Af17-/-mice exhibit defects in ENa C expression,renal Na+ retention,and blood pressure control.This review gives a brief summary of these novel findings.展开更多
Dravet syndrome is a rare epileptic encephalopathy characterized by frequent seizures beginning in the first year of life and behavioral disorders. Mutations in the sodium channel α1 subunit gene are the main cause o...Dravet syndrome is a rare epileptic encephalopathy characterized by frequent seizures beginning in the first year of life and behavioral disorders. Mutations in the sodium channel α1 subunit gene are the main cause of this disease. We report two patients with refractory seizures and psychomotor retardation in whom the final diagnosis was Dravet syndrome with confirmed mutations in the sodium channel α1 subunit gene. The mutation identified in the second patient was a novel frame shift mutation, which resulted from the deletion of five nucleotides in exon 24.展开更多
Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmat...Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.展开更多
Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present stud...Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.展开更多
Objectives Ischemia induced arrhythmia(ventricular tachycardia/ventricular fibrillation) is one of the major causes of death.Potassium channels change are likely to be responsible for the ischemia-related arrhythmias....Objectives Ischemia induced arrhythmia(ventricular tachycardia/ventricular fibrillation) is one of the major causes of death.Potassium channels change are likely to be responsible for the ischemia-related arrhythmias.Cardiac potassium current is the major outward current involved in cardiac repolarization.The properties of potassium channels have been intensively studied.Here,we investigated the association between ischemia induced arrhythmia and potassium channels genetic variations.Methods 23 patients with ventricular tachycardia/ventricular fibrillation induced by ischemia were selected as objects.5ML peripheral blood were taken from each person,from which DNA was extracted us- ing a standard enzymatic phenol-chloroform method.Candidate genes(HERG、KCNJ2、KCNQ1、Mink、Mirp1、Kir2.1、KV4.3、Kir3.1、KV1.5、Kir6.1、Kir6.2、Kir2.1) Were screened for potassium channels gene mutations with direct sequencing methods.Results Here 4 potassium channels gene mutations have been discovered.In the gene coding for the ATP-sensitive K^+ channels subunit Kir6.2,there is a change from valine to isoleucine at the position of 326(V326I).At the position 448,arginine substitutes proline(P448R) in the KC-NQ1 gene.In the gene KCNJ2 two mutations have been found(P156L,Q193H).Conclusions This study implicated that there is a high relationship between ischemia induced arrhythmia and the mutation of potassium channels.In order to identify the precisely relationship there is need functional analysis.展开更多
Understanding physiological responses in saline agriculture may facilitate wheat breeding programs.Based on a screening test,the Ningmai-14(NM-14)and Yangmai-23(YM-23)wheat cultivars were selected for further experime...Understanding physiological responses in saline agriculture may facilitate wheat breeding programs.Based on a screening test,the Ningmai-14(NM-14)and Yangmai-23(YM-23)wheat cultivars were selected for further experiments to understand the underlying salinity tolerance mechanism.This study investigated the effects of five salinity levels such as Control(CK)=0(without NaCl stress),S1=0.20%,S2=0.25%,S3=0.30%and S4=0.35%of NaCl concentrations of soil on wheat plants.The results showed that increased salinity concentration reduced the growth and yield of wheat cultivars(NM-14 and YM-23).However,YM-23(12.7%)yielded more than NM-14 at maximum salinity stress.The higher salinity(S4)increased the concentration of Na^(+)(4.3 to 5.8-fold)and P contents(2.5 to 2.2-fold),while reducing the average concentrations of K^(+),Cu,and K^(+)/Na^(+)ratio.The higher salinity(S4)reduced the spikelet length by 21.35%(followed by grain spike−1),and the starch content by 18.81%.In the YM-23 cultivar,higher salinity increased superoxide dismutase(SOD),total antioxidant capacity(TAC),and amylase.Compared to NM-14,induced expression of TaYUC2,6,and TaGA13ox,20ox genes were recorded in YM-23.Similarly,in YM-23 the stress-specific genes such as TaHSP70,90 were enhanced whereas,TaSOS1,2 were suppressed.Overall,our study revealed that salt tolerant cultivars modulate hormonal and antioxidant activities,thus maintaining high growth.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.
文摘The study titled“Transient receptor potential-related risk model predicts prognosis of hepatocellular carcinoma patients”is a significant contribution to hepatocellular carcinoma(HCC)research,highlighting the role of transient receptor potential(TRP)family genes in the disease’s progression and prognosis.Utilizing data from The Cancer Genome Atlas database,it establishes a new risk assessment model,emphasizing the interaction of TRP genes with tumor proliferation pathways,key metabolic reactions like retinol metabolism,and the tumor immune microenvironment.Notably,the overexpression of the TRPC1 gene in HCC correlates with poorer patient survival outcomes,suggesting its potential as a prognostic biomarker and a target for personalized therapy,particularly in strategies combining immunotherapy and anti-TRP agents.
基金Supported by the Program of the Network-type Joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University,Nagasaki University.
文摘BACKGROUND ATP sensitive K+(K_(ATP))channels are ubiquitously distributed in various of cells and tissues,including the liver.They play a role in the pathogenesis of myocardial and liver ischemia.AIM To evaluate the radiation-induced changes in the expression of K_(ATP)channel subunits in the mouse liver to understand the potential role of K_(ATP)channels in radiation injury.METHODS Adult C57BL/6 mice were randomly exposed toγ-rays at 0 Gy(control,n=2),0.2 Gy(n=6),1 Gy(n=6),or 5 Gy(n=6).The livers were removed 3 and 24 h after radiation exposure.Hematoxylin and eosin staining was used for morphological observation;immunohistochemical staining was applied to determine the expression of K_(ATP)channel subunits in the liver tissue.RESULTS Compared with the control group,the livers exposed to 0.2 Gyγ-ray showed an initial increase in the expression of Kir6.1 at 3 h,followed by recovery at 24 h after exposure.Exposure to a high dose of 5.0 Gy resulted in decreased expression of Kir6.1 and increased expression of SUR2B at 24 h.However,the expression of Kir6.2,SUR1,or SUR2A had no remarkable changes at 3 and 24 h after exposure to any of these doses.CONCLUSION The expression levels of Kir6.1 and SUR2B in mouse liver changed differently in response to different radiation doses,suggesting a potential role for them in radiation-induced liver injury.
文摘TWIK-related acid-sensitive K+(TASK) channels give rise to leak K+ currents which influence the resting membrane potential and input resistance. The wide expression of TASK1 and TASK3 channels in the central nervous system suggests that these channels are critically involved in neurological disorders. It has become apparent in the past decade that TASK channels play critical roles for the development of various neurological disorders. In this review, I describe evidence for their roles in ischemia, epilepsy, learning/memory/cognition and apoptosis.
文摘The shear stress distribution in circular channels was modeled in this study using gene expression programming(GEP). 173 sets of reliable data were collected under four flow conditions for use in the training and testing stages. The effect of input variables on GEP modeling was studied and 15 different GEP models with individual, binary, ternary, and quaternary input combinations were investigated. The sensitivity analysis results demonstrate that dimensionless parameter y/P, where y is the transverse coordinate, and P is the wetted perimeter, is the most influential parameter with regard to the shear stress distribution in circular channels. GEP model 10, with the parameter y/P and Reynolds number(Re) as inputs, outperformed the other GEP models, with a coefficient of determination of 0.7814 for the testing data set. An equation was derived from the best GEP model and its results were compared with an artificial neural network(ANN) model and an equation based on the Shannon entropy proposed by other researchers. The GEP model, with an average RMSE of 0.0301, exhibits superior performance over the Shannon entropy-based equation, with an average RMSE of 0.1049, and the ANN model, with an average RMSE of 0.2815 for all flow depths.
基金supported by the National Natural Science Foundation of China (30490251)
文摘The Cl^- homeostasis was known as the major mechanism of soybean to achieve NaCl tolerance, but studies on the role of chloride channel under abiotic stress were relatively few. We cloned a putative CLC-type chloride channel gene GmCLCnt from soybean via RACE and it was predicted to encode a protein of 783 amino acids with 9 possible transmembrane domains and 2 tandem CBS domains. Real-time RT-PCR analysis showed that the GmCLCnt gene was expressed in all tissues of soybean but enriched in leaves and its expression was induced by NaCl, polyethylene glycol （PEG）, coldness and ABA treatments. The Arabidopsis seedlings overexpressing GmCLCnt were more tolerant to higher concentration of NaCl than those of wild type. The results suggested that the GmCLCnt may be a CLC-type chloride channel and play an important role in salt tolerance.
基金supported by a grant from the National Natural Sciences Foundation of China (No. 30671743)
文摘The roles of voltage-dependent K^＋ channels during activation and damage in alveolar macrophages （AMs） exposed to different silica particles were examined. Rat AMs were collected by means of bronchoalveolar lavage, and were adjusted to 5× 10^5/mL. After AMs were exposed to different concentrations （0, 25, 50, 100, 200 μg/mL） of quartz particles and 100 μg/mL amorphous silica particles for 24 h, the voltage-depended K^＋ current in AMs was measured by using patch clamp technique. Meanwhile the leakage of lactate dehydrogenase （LDH） and the viability of AMs were detected respectively. Patch clamp studies demonstrated that AMs possessed outward delayed and inward rectifying K^＋ current. Exposure to quartz particles increased the outward delayed K^＋ current but it had no effect on inward rectifier K^＋ current in AMs. Neither of the two K^＋ channels in AMs was affected by amorphous silica particles. Cytotoxicity test showed that both silica particles could damage AM membrane and result in significant leakage of LDH （P〈0.05）. MTT studies, however, showed that only quartz particles reduced viability of AMs （P〈0.05）. It is concluded that quartz parti- cles can activate the outward delayed K^＋ channel in AMs, which may act as an activating signal in AMs to initiate an inflammatory response during damage and necrosis in AMs induced by exposure to quartz particle. K^＋ channels do not contribute to the membrane damage of AMs.
基金Supported by the Program of the network-type joint Usage/Research Center for Radiation Disaster Medical Science of Hiroshima University,Nagasaki University,and Fukushima Medical University
文摘BACKGROUND ATP-sensitive K^+(KATP)channels were originally found in cardiac myocytes by Noma in 1983.KATP channels were formed by potassium ion-passing poreforming subunits(Kir6.1,Kir6.2)and regulatory subunits SUR1,SU2A and SUR2B.A number of cells and tissues have been revealed to contain these channels including hepatocytes,but detailed localization of these subunits in different types of liver cells was still uncertain.AIM To investigate the expression of KATP channel subunits in rat liver and their localization in different cells of the liver.METHODS Rabbit anti-rat SUR1 peptide antibody was raised and purified by antigen immunoaffinity column chromatography.Four of Sprague-Dawley rats were used for liver protein extraction for immunoblot analysis,seven of them were used for immunohistochemistry both for the ABC method and immunofluorescence staining.Four of Wistar rats were used for the isolation of hepatic stellate cells(HSCs)and Kupffer cells for both primary culture and immunocytochemistry.RESULTS Immunoblot analysis showed that the five kinds of KATP channel subunits,i.e.Kir6.1,Kir6.2,SUR1,SUR2A,and SUR2B,were detected in liver.Immunohistochemical staining showed that Kir6.1 and Kir6.2 were weakly to moderately expressed in parenchymal cells and sinusoidal lining cells,while SUR1,SUR2A,and SUR2B were mainly localized to sinusoidal lining cells,such as HSCs,Kupffer cells,and sinusoidal endothelial cells.Immunoreactivity for SUR2A and SUR2B was expressed in the hepatocyte membrane.Double immunofluorescence staining further showed that the pore-forming subunits Kir6.1 and/or Kir6.2 colocalized with GFAP in rat liver sections and primary cultured HSCs.These KATP channel subunits also colocalized with CD68 in liver sections and primary cultured Kupffer cells.The SUR subunits colocalized with GFAP in liver sections and colocalized with CD68 both in liver sections and primary cultured Kupffer cells.In addition,five KATP channel subunits colocalized with SE-1 in sinusoidal endothelial cells.CONCLUSION Observations from the present study indicated that KATP channel subunits expressed in rat liver and the diversity of KATP channel subunit composition might form different types of KATP channels.This is applicable to hepatocytes,HSCs,various types of Kupffer cells and sinusoidal endothelial cells.
基金Supported by National Institutes of Health Grant 2R01 DK080236 06A1
文摘The epithelial Na+ channel(ENa C) consists of α,β,γsubunits.Its expression and function are regulated by aldosterone at multiple levels including transcription.ENa C plays a key role in Na+ homeostasis and blood pressure.Mutations in ENa C subunit genes result in hypertension or hypotension,depending on the nature of the mutations.Transcription of αENa C is considered as the rate-limiting step in the formation of functional ENa C.As an aldosterone target gene,αENa C is activated upon aldosterone-mineralocorticoid receptor binding to the cis-elements in the αENa C promoter,which is packed into chromatin.However,how aldosterone alters chromatin structure to induce changes in transcription is poorly understood.Studies by others and us suggest that Dot1a-Af9 complex represses αENa C by directly binding and regulating targeted histone H3 K79 hypermethylation at the specific subregions of αENa C promoter.Aldosterone decreases Dot1a-Af9 formation by impairing expression of Dot1 a and Af9 and by inducing Sgk1,which,in turn,phosphorylates Af9 at S435 to weaken Dot1a-Af9 interaction.MR attenuates Dot1aAf9 effect by competing with Dot1 a for binding Af9.Af17 relieves repression by interfering with Dot1a-Af9 interaction and promoting Dot1 a nuclear export.Af17-/-mice exhibit defects in ENa C expression,renal Na+ retention,and blood pressure control.This review gives a brief summary of these novel findings.
文摘Dravet syndrome is a rare epileptic encephalopathy characterized by frequent seizures beginning in the first year of life and behavioral disorders. Mutations in the sodium channel α1 subunit gene are the main cause of this disease. We report two patients with refractory seizures and psychomotor retardation in whom the final diagnosis was Dravet syndrome with confirmed mutations in the sodium channel α1 subunit gene. The mutation identified in the second patient was a novel frame shift mutation, which resulted from the deletion of five nucleotides in exon 24.
文摘Objective To characterize a novel frameshift mutation of the epithelial sodium channel(ENaC)βsubunit in a Chinese family with clinical suspicion of Liddle syndrome.And to emphasize that genetic testing is a confirmatory evidence of the diagnosis of Liddle syndrome.Methods DNA samples from the proband with early-onset,treatment-resistant hypertension and hypokalemia and 31 additional relatives were all sequenced for mutations in exon 13 of theβ-ENaC andγ-ENaC genes,using amplification by polymerase chain reaction and direct DNA sequencing.
基金supported by the Research Basis Formation Supporting Project for Private University
文摘Transient receptor potential channel A1 is one of the important transducers of noxious stimuli in the primary afferents, which may contribute to generation of neurogenic inflammation and hyperalgesia. The present study was designed to investigate if activation of transient receptor potential channel A1 may induce calcitonin gene-related peptide release from the primary afferent neurons. We found that application of allyl isothiocyanate, a transient receptor potential channel A1 activator, caused calcitonin gene-related peptide release from the cultured rat dorsal root ganglion neurons. Knock- down of transient receptor potential channel A1 with an antisense oligodeoxynucleotide prevented calcitonin gene-related peptide release by allyl isothiocyanate application in cultured dorsal root ganglion neurons. Thus, we concluded that transient receptor potential channel A1 activation caused calcitonin gene-related peptide release in sensory neurons.
文摘Objectives Ischemia induced arrhythmia(ventricular tachycardia/ventricular fibrillation) is one of the major causes of death.Potassium channels change are likely to be responsible for the ischemia-related arrhythmias.Cardiac potassium current is the major outward current involved in cardiac repolarization.The properties of potassium channels have been intensively studied.Here,we investigated the association between ischemia induced arrhythmia and potassium channels genetic variations.Methods 23 patients with ventricular tachycardia/ventricular fibrillation induced by ischemia were selected as objects.5ML peripheral blood were taken from each person,from which DNA was extracted us- ing a standard enzymatic phenol-chloroform method.Candidate genes(HERG、KCNJ2、KCNQ1、Mink、Mirp1、Kir2.1、KV4.3、Kir3.1、KV1.5、Kir6.1、Kir6.2、Kir2.1) Were screened for potassium channels gene mutations with direct sequencing methods.Results Here 4 potassium channels gene mutations have been discovered.In the gene coding for the ATP-sensitive K^+ channels subunit Kir6.2,there is a change from valine to isoleucine at the position of 326(V326I).At the position 448,arginine substitutes proline(P448R) in the KC-NQ1 gene.In the gene KCNJ2 two mutations have been found(P156L,Q193H).Conclusions This study implicated that there is a high relationship between ischemia induced arrhythmia and the mutation of potassium channels.In order to identify the precisely relationship there is need functional analysis.
基金the National Natural Science Foundation of China(32101817)Jiangsu Agriculture Science and this work was funded by the National Natural Science Foundation of China(32101817)+3 种基金Jiangsu Agriculture Science and Technology Innovation Fund(CX(21)3111)the Natural Science Foundation of the Jiangsu Higher Education Institutions(21KJD210001)the Scientific and Technological Innovation Fund of Carbon Emissions Peak and Neutrality of Jiangsu Provincial Department of Science and Technology(BE2022304)the project funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions(PAPD)for their financial support.
文摘Understanding physiological responses in saline agriculture may facilitate wheat breeding programs.Based on a screening test,the Ningmai-14(NM-14)and Yangmai-23(YM-23)wheat cultivars were selected for further experiments to understand the underlying salinity tolerance mechanism.This study investigated the effects of five salinity levels such as Control(CK)=0(without NaCl stress),S1=0.20%,S2=0.25%,S3=0.30%and S4=0.35%of NaCl concentrations of soil on wheat plants.The results showed that increased salinity concentration reduced the growth and yield of wheat cultivars(NM-14 and YM-23).However,YM-23(12.7%)yielded more than NM-14 at maximum salinity stress.The higher salinity(S4)increased the concentration of Na^(+)(4.3 to 5.8-fold)and P contents(2.5 to 2.2-fold),while reducing the average concentrations of K^(+),Cu,and K^(+)/Na^(+)ratio.The higher salinity(S4)reduced the spikelet length by 21.35%(followed by grain spike−1),and the starch content by 18.81%.In the YM-23 cultivar,higher salinity increased superoxide dismutase(SOD),total antioxidant capacity(TAC),and amylase.Compared to NM-14,induced expression of TaYUC2,6,and TaGA13ox,20ox genes were recorded in YM-23.Similarly,in YM-23 the stress-specific genes such as TaHSP70,90 were enhanced whereas,TaSOS1,2 were suppressed.Overall,our study revealed that salt tolerant cultivars modulate hormonal and antioxidant activities,thus maintaining high growth.
