NBCe2 (Slc4a5) Is Expressed in the Renal Connecting Tubules and Cortical Collecting Ducts and Mediates Base Extrusion

Barbuskaite, Dagne; Pedersen, Fredrik; Christensen, Henriette; Johnsen, Laura; Prætorius, Jeppe; Damkier, Helle Hasager

doi:10.3389/fphys.2020.00560

Cited by 10 publications

(8 citation statements)

References 35 publications

(58 reference statements)

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“…The electrogenic Na/HCO 3 cotransporter NBCe1 (SLC4A4) is the founding member of this SLC4 subfamily and is highly expressed in the kidneys, digestive system, and brain. 8 NBCe2 (SLC4A5), another electrogenic NBC, is mainly found in the liver, testis, and spleen 9 ; its physiologic importance has been addressed in the kidney 10 and choroid plexus. 11 NBCn1 (SLC4A7), an electroneutral NBC, is plentiful not only in skeletal muscle and heart 12 but also in epithelia ( e.g.…”

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confidence: 99%

Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Lee

Occhipinti

Moss

et al. 2022

JASN

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BackgroundDifferentiating among HCO3−, CO3=, and H+movements across membranes has long seemed impossible. We now seek to discriminate unambiguously among three alternate mechanisms: the inward flux of 2 HCO3−(mechanism 1), the inward flux of 1 CO3=(mechanism 2), and the CO2/HCO3−-stimulated outward flux of 2 H+(mechanism 3).MethodsAs a test case, we use electrophysiology and heterologous expression inXenopusoocytes to examine SLC4 family members that appear to transport “bicarbonate” (“HCO3−”).ResultsFirst, we note that cell-surface carbonic anhydrase should catalyze the forward reaction CO2+OH–→HCO3−if HCO3−is the substrate; if it is not, the reverse reaction should occur. Monitoring changes in cell-surface pH (ΔpHS) with or without cell-surface carbonic anhydrase, we find that the presumed Cl-“HCO3” exchanger AE1 (SLC4A1) does indeed transport HCO3−(mechanism 1) as long supposed, whereas the electrogenic Na/“HCO3” cotransporter NBCe1 (SLC4A4) and the electroneutral Na+-driven Cl-“HCO3” exchanger NDCBE (SLC4A8) do not. Second, we use mathematical simulations to show that each of the three mechanisms generates unique quantities of H+at the cell surface (measured asΔpHS) per charge transported (measured as change in membrane current,ΔIm). Calibrating ΔpHS/ΔImin oocytes expressing the H+channel HV1, we find that our NBCe1 data align closely with predictions of CO3=transport (mechanism 2), while ruling out HCO3−(mechanism 1) and CO2/HCO3−-stimulated H+transport (mechanism 3).ConclusionsOur surface chemistry approach makes it possible for the first time to distinguish among HCO3−, CO3=, and H+fluxes, thereby providing insight into molecular actions of clinically relevant acid-base transporters and carbonic-anhydrase inhibitors.

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confidence: 99%

Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Lee

Occhipinti

Moss

et al. 2022

JASN

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“…In a population survey, it was found that people with hypertension have a higher risk of gallstones than the general population, which may be related to the mutation of SLC4A5 gene loci ( Song et al, 2020 ). A number of studies have pointed out that there is a genetic association between SLC4A5 gene polymorphism and hypertension ( Parker, 2018 ; Barbuskaite et al, 2020 ). A healthy diet can reduce the risk of gallstone disease while preventing high blood pressure ( Wirth et al, 2018 ).…”

Section: Discussionmentioning

confidence: 99%

Association Study Between Polymorphic Loci in Cholesterol Metabolism Pathway and Gallstone in the Tibetan Population

Chen

Zhang

et al. 2022

Front. Genet.

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Background: The incidence of gallstones in the Tibetan population is increasing rapidly. Previous studies indicated that genetic variation located in the cholesterol metabolism pathway may be associated with the incidence of gallstones.Methods: By recruiting 132 Tibetan gallstone patients and 52 normal Tibetan controls, we performed next-generation sequencing for 508 genes in the cholesterol metabolism pathway. Additionally, by integrating the sequence data of 41 normal Tibetan subjects in the public database, we finally obtained 93 normal Tibetan controls. Single nucleotide polymorphisms (SNPs) calling were performed by using the GATK pipeline. The quality control criteria for SNPs were: missing rate <0.05; minor allele frequency (MAF) > 0.01; and p value >0.001 in the Hardy-Weinberg Equilibrium (HWE) test. To eliminate the influence of population heterogeneity, Principal Component Analysis (PCA) was carried out by using the smartpca software. Association analyses were performed by Plink software. Multiple tests were adjusted by the false discovery rate (FDR) method.Results: A total of 2,401 SNPs were obtained by analyzing 508 genes, and 2,011 SNPs left after quality control. After adjusting the eigen vectors, we found that 10 SNPs (SNV05997, rs80145081, rs80005560, rs79074685, rs748546375, rs201880593, rs142559357, rs750769471, rs869789 and rs4072341) were significantly associated with gallstone. Subsequently, by comparing the case group with our control group and the public database control group separately, we further found that the SNP rs869789 was consistently significantly associated with gallstone (p = 9.04 × 10–3 in cases vs. our controls and 5.73 × 10–3 in cases vs. public controls, respectively).Conclusion: By systematically analyzed SNPs in the cholesterol metabolism pathway, we identified one polymorphic locus rs869789 significantly associated with the pathogenesis of gallstone in the Tibetan population. This study will provide clue for further mechanism study of gallstone in the Tibetan population.

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“…A related function of MFAP5 is that it can remodel extracellular matrixes that may play a role in supporting hESC growth [ 19 ]. A protein that transports sodium and bicarbonate across the cell membrane as well as regulates cellular pH is encoded through SLC4A5 [ 20 ]. ADAMTS-4 is a metalloprotease that plays a role in aggrecan degradation in an extracellular matrix [ 21 ].…”

Section: Discussionmentioning

confidence: 99%

Different transcriptional profiles of human embryonic stem cells grown in a feeder-free culture system and on human foreskin fibroblast feeder layers

Jun

Liu

et al. 2022

Aging

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Feeder cells provide an optimal microenvironment for the propagation of human embryonic stem cells (hESCs) by supplying currently known or unknown factors. However, the hESCs grown on feeder cells are not suitable for the purpose of clinical application because of the risk of contamination. In recent years, the feeder-free culture method has been developed to eliminate contamination, but some studies show that hESCs exhibit poor growth patterns in a feeder-free culture system. Regarding this phenomenon, we speculate that some genes related to hESC propagation were differently expressed in hESCs grown on feeder cells. To test this hypothesis, 3 hESC lines (NF4, NF5 and P096) were efficiently expanded in a feeder-free culture system or on human foreskin fibroblast (HFF) cells. The different gene expression patterns of hESCs in these 2 conditions were analyzed through microarrays. The results revealed that the hESCs cultured in both conditions maintained the expression of stemness markers and the ability to spontaneously differentiate into the 3 germ layers. The analysis of gene expression profiles revealed that 23 lncRNA and 15 genes were significantly differentially expressed in these two culture conditions. Furthermore, GO analyses showed that these genes were involved in such biological processes as growth factor stimuli, cell growth, and stem cell maintenance. To summarize, our study demonstrated that the hESCs grown on the HFF showed different gene expression patterns compared to those grown in a feeder-free culture system, suggesting that these differently expressed lncRNAs and genes played important roles in maintaining hESC propagation.

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NBCe2 (Slc4a5) Is Expressed in the Renal Connecting Tubules and Cortical Collecting Ducts and Mediates Base Extrusion

Cited by 10 publications

References 35 publications

Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Distinguishing among HCO3 −, CO3 =, and H+ as Substrates of Proteins That Appear To Be “Bicarbonate” Transporters

Association Study Between Polymorphic Loci in Cholesterol Metabolism Pathway and Gallstone in the Tibetan Population

Different transcriptional profiles of human embryonic stem cells grown in a feeder-free culture system and on human foreskin fibroblast feeder layers

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