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
In a recent study published in Science,Hicks et al.utilized Mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically(MIDAS)to explore protein-metabolite interactome and have...In a recent study published in Science,Hicks et al.utilized Mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically(MIDAS)to explore protein-metabolite interactome and have revealed previously unknown regulation for lactate dehydrogenase.1 This report brings an exciting new approach to address a long-standing challenge in biology.Cellular functions are orchestrated by an interactive network of molecular constituents,the physical interactions between proteins and other molecular entities,such as DNA,RNA,and metabolites.Like basic vocabulary for the book of life,these interactions are the fundamental mechanisms for complex physiology and diseases.展开更多
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In a recent study published in Science,Hicks et al.utilized Mass spectrometry integrated with equilibrium dialysis for the discovery of allostery systematically(MIDAS)to explore protein-metabolite interactome and have revealed previously unknown regulation for lactate dehydrogenase.1 This report brings an exciting new approach to address a long-standing challenge in biology.Cellular functions are orchestrated by an interactive network of molecular constituents,the physical interactions between proteins and other molecular entities,such as DNA,RNA,and metabolites.Like basic vocabulary for the book of life,these interactions are the fundamental mechanisms for complex physiology and diseases.
