Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic an...Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.展开更多
The purpose of this study was to evaluate the ability of aqueous extract of Aloe barbadensis Miller (Aloe vera) on oxidative damage and Anion Exchanger 1 (AE1, also known as Band 3) expression in human erythrocytes ex...The purpose of this study was to evaluate the ability of aqueous extract of Aloe barbadensis Miller (Aloe vera) on oxidative damage and Anion Exchanger 1 (AE1, also known as Band 3) expression in human erythrocytes exposed to the water soluble free radical initiator 2.2’-azobis-2-amidinopropano dihydrochloride (AAPH). In addition, total phenolic compounds in the extracts were determined as catechin equivalent and the various antioxidant activities were compared to natural and synthetic standard antioxidants such as BHA and ascorbic acid. Since Aloe vera extract did not cause a consumption of the cytosolic antioxidant, glutathione (GSH) when it was direct incubated with GSH in basic aerated aqueous solution, this indicates that Aloe vera extract does not proceed auto oxidation at this experimental condition. Furthermore, Aloe vera extract prevent the consumption of GSH, in radical treated RBCs. It also inhibit consumption of GSH when it was direct incubated with AAPH. Aloe vera gel extract inhibits the generation of diphenyl-2-picrylhy-drazyl (DPPH) and the scavenging activity was increased in a dose dependent manner. Aloe vera extract was shown the similar reducing power than standards BHT and ascorbic acid. Biochemical analysis by SDS-PAGE and western blotting showed that AAPH-induced oxidative stress increased the susceptibility of AE1 to proteolytic degradation. Of note, our data evidenced that Aloe vera treatment was able to partially restore the normal RBC membrane protein profiles in a dose-dependent manner. These results clearly demonstrate the antioxidative activity of Aloe vera gel extract that might be ascribed to a synergistic action of the bioactive compounds contained therein.展开更多
基金Supported by National Institutes of Health Grants HL061974 to Shull GEand ES017263 to Wang HS
文摘Bicarbonate is one of the major anions in mammalian tissues and extracellular fluids. Along with accompanying H+, HCO3- is generated from CO2 and H2 O, either spontaneously or via the catalytic activity of carbonic anhydrase. It serves as a component of the major buffer system, thereby playing a critical role in pH homeostasis. Bicarbonate can also be utilized by a variety of ion transporters, often working in coupled systems, to transport other ions and organic substrates across cell membranes. The functions of HCO3- and HCO3--transporters in epithelial tissues have been studied extensively, but their functions in heart are less well understood. Here we review studies of the identities and physiological functions of Cl-/HCO3- exchangers and Na+/HCO3-cotransporters of the SLC4 A and SLC26 A families in heart. We also present RNA Seq analysis of their cardiac mRNA expression levels. These studies indicate that slc4a3(AE3) is the major Cl-/HCO3- exchanger and plays a protective role in heart failure, and that Slc4a4(NBCe1) is the major Na+/HCO3- cotransporter and affects action potential duration. In addition, previous studies show that HCO3- has a positive inotropic effect in the perfused heart that is largely independent of effects on intracellular Ca2+. The importance of HCO3- in the regulation of contractility is supported by experiments showing that isolated cardiomyocytes exhibit sharply enhanced contractility, with no change in Ca2+ transients, when switched from Hepes-buffered to HCO3-- buffered solutions. These studies demonstrate that HCO3- and HCO3--handling proteins play important roles in the regulation of cardiac function.
文摘The purpose of this study was to evaluate the ability of aqueous extract of Aloe barbadensis Miller (Aloe vera) on oxidative damage and Anion Exchanger 1 (AE1, also known as Band 3) expression in human erythrocytes exposed to the water soluble free radical initiator 2.2’-azobis-2-amidinopropano dihydrochloride (AAPH). In addition, total phenolic compounds in the extracts were determined as catechin equivalent and the various antioxidant activities were compared to natural and synthetic standard antioxidants such as BHA and ascorbic acid. Since Aloe vera extract did not cause a consumption of the cytosolic antioxidant, glutathione (GSH) when it was direct incubated with GSH in basic aerated aqueous solution, this indicates that Aloe vera extract does not proceed auto oxidation at this experimental condition. Furthermore, Aloe vera extract prevent the consumption of GSH, in radical treated RBCs. It also inhibit consumption of GSH when it was direct incubated with AAPH. Aloe vera gel extract inhibits the generation of diphenyl-2-picrylhy-drazyl (DPPH) and the scavenging activity was increased in a dose dependent manner. Aloe vera extract was shown the similar reducing power than standards BHT and ascorbic acid. Biochemical analysis by SDS-PAGE and western blotting showed that AAPH-induced oxidative stress increased the susceptibility of AE1 to proteolytic degradation. Of note, our data evidenced that Aloe vera treatment was able to partially restore the normal RBC membrane protein profiles in a dose-dependent manner. These results clearly demonstrate the antioxidative activity of Aloe vera gel extract that might be ascribed to a synergistic action of the bioactive compounds contained therein.