A simple strategy of Cu modification was proposed to broaden the operation temperature window for NbCe catalyst.The best catalyst Cu0.010/Nb1Ce3 presented over 90%NO conversion in a wide temperature range of 200-400℃...A simple strategy of Cu modification was proposed to broaden the operation temperature window for NbCe catalyst.The best catalyst Cu0.010/Nb1Ce3 presented over 90%NO conversion in a wide temperature range of 200-400℃and exhibited an excellent H_(2)O or/and SO_(2) resistance at 275℃.To understand the promotional mechanism of Cu modification,the correlation among the"activity-structure-property"were tried to establish systematically.Cu species highly dispersed on NbCe catalyst to serve as the active component.The strong interaction among Cu,Nb and Ce promoted the emergence of NbO4 and induced more Bronsted acid sites.And Cu modification obviously enhanced the redox behavior of the NbCe catalyst.Besides,EPR probed the Cu species exited in the form of monomeric and dimeric Cu^(2+),the isolated Cu^(2+)acted as catalytic active sites to promote the reaction:Cu^(2+)-NO_(3)^(-)+NO(g)→Cu^(2+)-NO_(2)^(-)+NO_(2)(g).Then the generated NO_(2) would accelerate the fast-SCR reaction process and thus facilitated the lowtemperature deNO_(x) efficiency.Moreover,surface nitrates became unstable and easy to decompose after Cu modification,thus providing additional adsorption and activation sites for NH3,and ensuring the improvement of catalytic activity at high temperature.Since the NH3-SCR reaction followed by E-R reaction pathway efficaciously over Cu_(0.010)/Nb_(1)Ce_(3) catalyst,the excellent H_(2)O and SO_(2) resistance was as expected.展开更多
AIM To investigate the hypothesis that cardiomyocytespecific loss of the electrogenic NBCe1 Na^+-HCO3^- cotransporter is cardioprotective during in vivo ischemiareperfusion(IR)injury.METHODS An NBCe1 (Slc4a4 gene) con...AIM To investigate the hypothesis that cardiomyocytespecific loss of the electrogenic NBCe1 Na^+-HCO3^- cotransporter is cardioprotective during in vivo ischemiareperfusion(IR)injury.METHODS An NBCe1 (Slc4a4 gene) conditional knockout mouse(KO)model was prepared by gene targeting.Cardiovascular performance of wildtype (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements,and changes in cardiac gene expression were determined by RNA Seq analysis.Response to in vivo IR injury was analyzed after 30 min occlusion of the left anterior descending artery followed by 3 h of reperfusion. RESULTS Loss of NBCe1 in cardiac myocytes did not impair cardiac contractility or relaxation under basal conditions or in response toβ-adrenergic stimulation,and caused only limited changes in gene expression patterns,such as those for electrical excitability.However,following ischemia and reperfusion,KO heart sections exhibited significantly fewer apoptotic nuclei than WT sections.CONCLUSION These studies indicate that cardiac-specific loss of NBCe1 does not impair cardiovascular performance,causes only minimal changes in gene expression patterns,and protects against IR injury in vivo.展开更多
The electrogenic Na+-HCO3– cotransporter NBCe1 encoded by SLC4A4 gene plays essential roles in the regulation of intracellular/extracellular pH. Three NBCe1 variants are thought to mediate distinct physiological role...The electrogenic Na+-HCO3– cotransporter NBCe1 encoded by SLC4A4 gene plays essential roles in the regulation of intracellular/extracellular pH. Three NBCe1 variants are thought to mediate distinct physiological roles with different modes of transport stoichiometry. Homozygous inactivating mutations in NBCe1 cause the isolated proximal renal tubular acidosis (pRTA) invariably associated with ocular abnormalities. Functional analyses indicate that more than 50% reduction in NBCe1 activity may be required to induce severe acidemia. Some of the pRTA- related NBCe1 mutations, which show defective me-mbrane expression in mammalian cells, are also associated with migraine. Dysregulation of local pH in brain due to the loss of NBCe1 activity in astrocytes may underlie this association. Two types of NBCe1 deficient animals, NBCe1 knockout and W516X knockin mice, have been reported. Both of them show severe acidemia and early lethality unless they are treated with alkali. In isolated renal proximal tubules from W516X knockin mice, both NBCe1 activity and the rate of bicarbonate absorption are severely reduced, confirming the essential role of NBCe1 in bicarbonate absorption from this nephron segment. In this review, we summarize the recent data about physiological and pathophysiological roles of NBCe1 in health and diseases.展开更多
The kidney plays quite an important role in the regulation of acid-base homeostasis. The dysfunction of renal acid-base regulation causes diseases such as developmental disorder, bone malformation, calcification of ey...The kidney plays quite an important role in the regulation of acid-base homeostasis. The dysfunction of renal acid-base regulation causes diseases such as developmental disorder, bone malformation, calcification of eye and brain, etc. In the kidney, this regulation is performed, to a considerable part, in the proximal tubule of the nephron. In the luminal side the key player is sodium-proton exchanger type 3 (NHE3), whereas sodium-bicarbonate cotransporter (NBCe1) plays the critical role in the basolateral side. In the cytoplasm there is carbonic anhydrase type 2 (CAII) that intermediates the conversion of CO2/ . Interestingly, in human, mutations have been found in NBCe1 and CAII but not in NHE3 so far. Mutations of NBCe1 lead to severe proximal renal tubular acidosis (pRTA) and other systemic manifestations. In animal model studies, however, the relative contribution of NHE3 to proximal tubule functions remains controversial. Recently, V-ATPase with renal specific subunits is suggested to have some roles in the regulation of proximal tubule functions. In this review, we will discuss the regulation of acid-base transport in the proximal tubule and the updates.展开更多
基金Financial support from the National Natural Science Foundation of China,China(Nos.21972062,21976081,21976111)。
文摘A simple strategy of Cu modification was proposed to broaden the operation temperature window for NbCe catalyst.The best catalyst Cu0.010/Nb1Ce3 presented over 90%NO conversion in a wide temperature range of 200-400℃and exhibited an excellent H_(2)O or/and SO_(2) resistance at 275℃.To understand the promotional mechanism of Cu modification,the correlation among the"activity-structure-property"were tried to establish systematically.Cu species highly dispersed on NbCe catalyst to serve as the active component.The strong interaction among Cu,Nb and Ce promoted the emergence of NbO4 and induced more Bronsted acid sites.And Cu modification obviously enhanced the redox behavior of the NbCe catalyst.Besides,EPR probed the Cu species exited in the form of monomeric and dimeric Cu^(2+),the isolated Cu^(2+)acted as catalytic active sites to promote the reaction:Cu^(2+)-NO_(3)^(-)+NO(g)→Cu^(2+)-NO_(2)^(-)+NO_(2)(g).Then the generated NO_(2) would accelerate the fast-SCR reaction process and thus facilitated the lowtemperature deNO_(x) efficiency.Moreover,surface nitrates became unstable and easy to decompose after Cu modification,thus providing additional adsorption and activation sites for NH3,and ensuring the improvement of catalytic activity at high temperature.Since the NH3-SCR reaction followed by E-R reaction pathway efficaciously over Cu_(0.010)/Nb_(1)Ce_(3) catalyst,the excellent H_(2)O and SO_(2) resistance was as expected.
基金Supported by NIH grants,No.HL061974(to Gary E Shull),No.R01HL136025(to Yigang Wang),No.P30ES006096(to Mario Medvedovic)funds from the Center for Clinical and Translational Science and Training,University of Cincinnati(to Gary E Shull)a Research Innovation Seed Grant from the University of Cincinnati(to Gary E Shull and John N Lorenz)
文摘AIM To investigate the hypothesis that cardiomyocytespecific loss of the electrogenic NBCe1 Na^+-HCO3^- cotransporter is cardioprotective during in vivo ischemiareperfusion(IR)injury.METHODS An NBCe1 (Slc4a4 gene) conditional knockout mouse(KO)model was prepared by gene targeting.Cardiovascular performance of wildtype (WT) and cardiac-specific NBCe1 KO mice was analyzed by intraventricular pressure measurements,and changes in cardiac gene expression were determined by RNA Seq analysis.Response to in vivo IR injury was analyzed after 30 min occlusion of the left anterior descending artery followed by 3 h of reperfusion. RESULTS Loss of NBCe1 in cardiac myocytes did not impair cardiac contractility or relaxation under basal conditions or in response toβ-adrenergic stimulation,and caused only limited changes in gene expression patterns,such as those for electrical excitability.However,following ischemia and reperfusion,KO heart sections exhibited significantly fewer apoptotic nuclei than WT sections.CONCLUSION These studies indicate that cardiac-specific loss of NBCe1 does not impair cardiovascular performance,causes only minimal changes in gene expression patterns,and protects against IR injury in vivo.
文摘The electrogenic Na+-HCO3– cotransporter NBCe1 encoded by SLC4A4 gene plays essential roles in the regulation of intracellular/extracellular pH. Three NBCe1 variants are thought to mediate distinct physiological roles with different modes of transport stoichiometry. Homozygous inactivating mutations in NBCe1 cause the isolated proximal renal tubular acidosis (pRTA) invariably associated with ocular abnormalities. Functional analyses indicate that more than 50% reduction in NBCe1 activity may be required to induce severe acidemia. Some of the pRTA- related NBCe1 mutations, which show defective me-mbrane expression in mammalian cells, are also associated with migraine. Dysregulation of local pH in brain due to the loss of NBCe1 activity in astrocytes may underlie this association. Two types of NBCe1 deficient animals, NBCe1 knockout and W516X knockin mice, have been reported. Both of them show severe acidemia and early lethality unless they are treated with alkali. In isolated renal proximal tubules from W516X knockin mice, both NBCe1 activity and the rate of bicarbonate absorption are severely reduced, confirming the essential role of NBCe1 in bicarbonate absorption from this nephron segment. In this review, we summarize the recent data about physiological and pathophysiological roles of NBCe1 in health and diseases.
文摘The kidney plays quite an important role in the regulation of acid-base homeostasis. The dysfunction of renal acid-base regulation causes diseases such as developmental disorder, bone malformation, calcification of eye and brain, etc. In the kidney, this regulation is performed, to a considerable part, in the proximal tubule of the nephron. In the luminal side the key player is sodium-proton exchanger type 3 (NHE3), whereas sodium-bicarbonate cotransporter (NBCe1) plays the critical role in the basolateral side. In the cytoplasm there is carbonic anhydrase type 2 (CAII) that intermediates the conversion of CO2/ . Interestingly, in human, mutations have been found in NBCe1 and CAII but not in NHE3 so far. Mutations of NBCe1 lead to severe proximal renal tubular acidosis (pRTA) and other systemic manifestations. In animal model studies, however, the relative contribution of NHE3 to proximal tubule functions remains controversial. Recently, V-ATPase with renal specific subunits is suggested to have some roles in the regulation of proximal tubule functions. In this review, we will discuss the regulation of acid-base transport in the proximal tubule and the updates.
