Mis-trafficking of bicarbonate transporters: implications to human diseasesThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (2) ◽  
pp. 157-177 ◽  
Author(s):  
Ensaf Y. Almomani ◽  
Carmen Y.S. Chu ◽  
Emmanuelle Cordat
Keyword(s):  
Peer Review Process ◽  
Waste Product ◽  
Gene Families ◽  
Acid Base Balance ◽  
Mammalian Cell Lines ◽  
Current State ◽  
Bicarbonate Transporters ◽  
Base Balance ◽  
Health And Disease ◽  
Selection Of

Bicarbonate is a waste product of mitochondrial respiration and one of the main buffers in the human body. Thus, bicarbonate transporters play an essential role in maintaining acid-base balance but also during fetal development as they ensure tight regulation of cytosolic and extracellular environments. Bicarbonate transporters belong to two gene families, SLC4A and SLC26A. Proteins from these two families are widely expressed, and thus mutations in their genes result in various diseases that affect bones, pancreas, reproduction, brain, kidneys, eyes, heart, thyroid, red blood cells, and lungs. In this minireview, we discuss the current state of knowledge regarding the effect of SLC4A and SLC26A mutants, with a special emphasis on mutants that have been studied in mammalian cell lines and how they correlate with phenotypes observed in mice models.

scholarly journals Sodium Transporters in Human Health and Disease

2021 ◽  
Vol 11 ◽  
Author(s):  
Kenneth B. Gagnon ◽  
Eric Delpire
Keyword(s):  
Human Health ◽  
Plasma Membranes ◽  
Transport Mechanisms ◽  
Acid Base Balance ◽  
Salt Wasting ◽  
Excitatory Neurotransmitters ◽  
Base Balance ◽  
Physiological Homeostasis ◽  
Health And Disease ◽  
Dependent Transport

Sodium (Na+) electrochemical gradients established by Na+/K+ ATPase activity drives the transport of ions, minerals, and sugars in both excitable and non-excitable cells. Na+-dependent transporters can move these solutes in the same direction (cotransport) or in opposite directions (exchanger) across both the apical and basolateral plasma membranes of polarized epithelia. In addition to maintaining physiological homeostasis of these solutes, increases and decreases in sodium may also initiate, directly or indirectly, signaling cascades that regulate a variety of intracellular post-translational events. In this review, we will describe how the Na+/K+ ATPase maintains a Na+ gradient utilized by multiple sodium-dependent transport mechanisms to regulate glucose uptake, excitatory neurotransmitters, calcium signaling, acid-base balance, salt-wasting disorders, fluid volume, and magnesium transport. We will discuss how several Na+-dependent cotransporters and Na+-dependent exchangers have significant roles in human health and disease. Finally, we will discuss how each of these Na+-dependent transport mechanisms have either been shown or have the potential to use Na+ in a secondary role as a signaling molecule.

Structural analysis of the Na+/H+ exchanger isoform 1 (NHE1) using the divide and conquer approachThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (2) ◽  
pp. 189-199 ◽  
Author(s):  
Brian L. Lee ◽  
Brian D. Sykes ◽  
Larry Fliegel
Keyword(s):  
Crystal Structure ◽  
Membrane Protein ◽  
Peer Review Process ◽  
Divide And Conquer ◽  
Transmembrane Helices ◽  
Transmembrane Segments ◽  
Sodium Proton Exchanger ◽  
Attractive Therapeutic Target ◽  
Health And Disease ◽  
Selection Of

The sodium/proton exchanger isoform 1 (NHE1) is an ubiquitous plasma membrane protein that regulates intracellular pH by removing excess intracellular acid. NHE1 is important in heart disease and cancer, making it an attractive therapeutic target. Although much is known about the function of NHE1, current structural knowledge of NHE1 is limited to two conflicting topology models: a low-resolution molecular envelope from electron microscopy, and comparison with a crystal structure of a bacterial homologue, NhaA. Our laboratory has used high-resolution nuclear magnetic resonance (NMR) spectroscopy to investigate the structures of individual transmembrane helices of NHE1 — a divide and conquer approach to the study of this membrane protein. In this review, we discuss the structural and functional insights obtained from this approach in combination with functional data obtained from mutagenesis experiments on the protein. We also compare the known structure of NHE1 transmembrane segments with the structural and functional insights obtained from a bacterial sodium/proton exchanger homologue, NhaA. The structures of regions of the NHE1 protein that have been determined have both similarities and specific differences to the crystal structure of the NhaA protein. These have allowed insights into both the topology and the function of the NHE1 protein.

Topology models of anion exchanger 1 that incorporate the anti-parallel V-shaped motifs found in the EM structureThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (2) ◽  
pp. 148-156 ◽  
Author(s):  
Teruhisa Hirai ◽  
Naotaka Hamasaki ◽  
Tomohiro Yamaguchi ◽  
Yohei Ikeda
Keyword(s):  
Anion Exchanger ◽  
Peer Review Process ◽  
Three Dimensional ◽  
Structural Similarity ◽  
Dimensional Structure ◽  
Membrane Bilayer ◽  
Anion Exchanger 1 ◽  
Advantages And Disadvantages ◽  
Health And Disease ◽  
Selection Of

We recently published the three-dimensional structure of the membrane domain of human erythrocyte anion exchanger 1 (AE1) at 7.5 Å resolution, solved by electron crystallography. The structure exhibited distinctive anti-parallel V-shaped motifs, which protrude from the membrane bilayer on both sides. Similar motifs exist in the previously reported structure of a bacterial chloride channel (ClC)-type protein. Here, we propose two topology models of AE1 that reflect the anti-parallel V-shaped structural motifs. One is assumed to have structural similarity with the ClC protein and the other is only assumed to have internal repeats, as is often the case with transporters. Both models are consistent with most topological results reported thus far for AE1, each having advantages and disadvantages.

Anion exchanger 1 in red blood cells and kidney: Band 3’s in a podThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (2) ◽  
pp. 106-114 ◽  
Author(s):  
Fiona Wu ◽  
Timothy J. Satchwell ◽  
Ashley M. Toye
Keyword(s):  
Review Process ◽  
Peer Review Process ◽  
Band 3 ◽  
Glomerular Filtration Barrier ◽  
Anion Exchanger 1 ◽  
Filtration Barrier ◽  
Kidney Glomerulus ◽  
Health And Disease ◽  
Distal Tubules ◽  
Selection Of

The bicarbonate/chloride exchanger 1 (AE1, Band 3) is abundantly expressed in the red blood cell membrane, where it is involved in gas exchange and functions as a major site of cytoskeletal attachment to the erythrocyte membrane. A truncated kidney isoform (kAE1) is highly expressed in type A intercalated cells of the distal tubules, where it is vital for urinary acidification. Recently, kAE1 has emerged as a novel physiologically significant protein in the kidney glomerulus. This minireview will discuss the known interactions of kAE1 in the podocytes and the possible mechanisms whereby this important multispanning membrane protein may contribute to the function of the glomerular filtration barrier and prevent proteinuria.

scholarly journals Selection of Arteries for Blood Sampling and Evaluation of Blood Gases and Acid-Base Balance in Cattle

2002 ◽  
Vol 71 (3) ◽  
pp. 289-296 ◽  
Author(s):  
O. Nagy ◽  
G. Kováč ◽  
H. Seidel ◽  
I. Paulíková
Keyword(s):  
Blood Gases ◽  
Blood Sampling ◽  
Acid Base Balance ◽  
Acid Base ◽  
Base Balance ◽  
Selection Of

scholarly journals Modeling Transport and Flow Regulatory Mechanisms of the Kidney

2012 ◽  
Vol 2012 ◽  
pp. 1-18 ◽  
Author(s):  
Anita T. Layton
Keyword(s):  
Tubuloglomerular Feedback ◽  
Regulatory Mechanisms ◽  
Electrolyte Balance ◽  
Acid Base Balance ◽  
Acid Base ◽  
Kidney Physiology ◽  
Base Balance ◽  
Modeling Transport ◽  
Health And Disease ◽  
Renal Oxygen

The kidney plays an indispensable role in the regulation of whole-organism water balance, electrolyte balance, and acid-base balance, and in the excretion of metabolic wastes and toxins. In this paper, we review representative mathematical models that have been developed to better understand kidney physiology and pathophysiology, including the regulation of glomerular filtration, the regulation of renal blood flow by means of the tubuloglomerular feedback mechanisms and of the myogenic mechanism, the urine concentrating mechanism, and regulation of renal oxygen transport. We discuss how such modeling efforts have significantly expanded our understanding of renal function in both health and disease.

scholarly journals Effects of Bicarbonate Stress on Serum Ions and Gill Transporters in Alkali and Freshwater Forms of Amur Ide (Leuciscus waleckii)

2021 ◽  
Vol 12 ◽  
Author(s):  
Yu Mei Chang ◽  
Xue Fei Zhao ◽  
Hon Jung Liew ◽  
Bo Sun ◽  
Shuang Yi Wang ◽  
...  
Keyword(s):  
Mrna Level ◽  
Freshwater Ecosystems ◽  
Comparative Approach ◽  
Mrna Levels ◽  
Acid Base Balance ◽  
Acid Base ◽  
Bicarbonate Transporters ◽  
Alkaline Conditions ◽  
Base Balance ◽  
Serum Ions

The Amur ide (Leuciscus waleckii) is a fish in the Cyprinidae family. Compared with other Amur ide living in freshwater ecosystems, the Amur ide population in Lake Dali Nor of China is famous for its high tolerance to the alkaline conditions of 54 mM (pH 9.6). Yet, surprisingly, the ionoregulatory mechanism responsible for this remarkable alkaline adaptation remains unclear. Therefore, this study sought to investigate how bicarbonate affects the acid-base balancing and ionoregulatory responses of this animal. Here, using a comparative approach, the alkali form of Amur ide and its ancestral freshwater form living in other freshwater basins were each exposed to 50 mM (pH 9.59 ± 0.09), a level close to the alkalinity of Lake Dali Nor, and their physiological (AE1) adjustment of ions and acid-base regulation were investigated. This study highlighted differences in blood pH and serum ions (e.g., Na+, K+, Cl−, and Ca2+), Na+/K+ ATPase (NKA) activity and its mRNA level, and mRNA expression of gill transporters (Na+/H+ exchanger member 2 and/or 3, Na+/HCO3- cotransporter (NBC1), Cl−/HCO3- exchanger, Na+/Cl− cotransporter (NCC), Na+/K+/2Cl− (NKCC1), SLC26A5, and SLC26A6) for alkalinity adaptation between the two forms of Amur ide differing in alkalinity tolerance. Specifically, close relationships among the serum Na+ and mRNA levels of NCC, NKCC1, and NHE, and also NKA and NBC1, in addition to serum Cl− and bicarbonate transporters (e.g., SLC26A5 and SLC26A6), characterized the alkali form of Amur ide. We propose that this ecotype can ensure its transepithelial Cl− and Na+ uptake/base secretions are highly functional, by its basolateral NKA with NBC1 and apical ionic transporters, and especially NCC incorporated with other transporters (e.g., SLC26). This suggests an evolved strong ability to maintain an ion osmotic and acid-base balance for more effectively facilitating its adaptability to the high alkaline environment. This study provides new insights into the physiological responses of the alkaline form of the Amur ide fish for adapting to extreme alkaline conditions. This information could be used as a reference to cultivating alkaline-tolerant fish species in abandoned alkaline waters.

Structural comparison of substrate entry gate for rhomboid intramembrane peptidasesThis paper is one of a selection of papers published in a Special Issue entitled CSBMCB 53rd Annual Meeting — Membrane Proteins in Health and Disease, and has undergone the Journal’s usual peer review process.

2011 ◽  
Vol 89 (2) ◽  
pp. 216-223 ◽  
Author(s):  
Christelle Lazareno-Saez ◽  
Cory L. Brooks ◽  
M. Joanne Lemieux
Keyword(s):  
Membrane Proteins ◽  
Hydrophobic Interactions ◽  
Peer Review Process ◽  
Mobile Element ◽  
Transmembrane Helices ◽  
General Role ◽  
E Coli ◽  
Signalling Molecules ◽  
Health And Disease ◽  
Selection Of

Rhomboids are intramembrane serine peptidases conserved in all kingdoms of life. Their general role is to cleave integral membrane proteins to release signalling molecules. These signals, when disrupted, can contribute to various diseases. Crystal structures of H. influenzae (hiGlpG) and E. coli GlpG (ecGlpG) rhomboids have revealed a structure with six transmembrane helices and a Ser–His catalytic dyad buried within the membrane. One emerging issue was the identification of the mobile element in the protein that allows substrate docking. It has been proposed that the substrate entry gate is composed of helix 5 and loop 5. The present review studies the structures of these two orthologs. In ecGlpG structures, different conformations of loop 5 and helix 5 are observed. Open and closed conformations of ecGlpG structures are compared with each other and with hiGlpG, surveying differences in hydrophobic interactions within loop 5 and helix 5. Furthermore, a comparison of the ecGlpG and hiGlpG structures reveals differences in loop 4. Overall, less variation is observed in loop 4, suggesting this region acts as an anchor for the substrate gate. Functional and regulatory implications of these variations are discussed.

Higher Dietary Acidity is Associated with Lower Bone Mineral Density in Postmenopausal Iranian Women, Independent of Dietary Calcium Intake

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0206-0217 ◽  
Author(s):  
Seyedeh-Elaheh Shariati-Bafghi ◽  
Elaheh Nosrat-Mirshekarlou ◽  
Mohsen Karamati ◽  
Bahram Rashidkhani
Keyword(s):  
Calcium Intake ◽  
Dietary Calcium ◽  
Dietary Calcium Intake ◽  
Dietary Intakes ◽  
Iranian Women ◽  
Acid Base Balance ◽  
Mineral Density ◽  
Acid Base ◽  
Base Balance ◽  
Dietary Acid

Findings of studies on the link between dietary acid-base balance and bone mass are relatively mixed. We examined the association between dietary acid-base balance and bone mineral density (BMD) in a sample of Iranian women, hypothesizing that a higher dietary acidity would be inversely associated with BMD, even when dietary calcium intake is adequate. In this cross-sectional study, lumbar spine and femoral neck BMDs of 151 postmenopausal women aged 50 - 85 years were measured using dual-energy x-ray absorptiometry. Dietary intakes were assessed using a validated food frequency questionnaire. Renal net acid excretion (RNAE), an estimate of acid-base balance, was then calculated indirectly from the diet using the formulae of Remer (based on dietary intakes of protein, phosphorus, potassium, and magnesium; RNAERemer) and Frassetto (based on dietary intakes of protein and potassium; RNAEFrassetto), and was energy adjusted by the residual method. After adjusting for potential confounders, multivariable adjusted means of the lumbar spine BMD of women in the highest tertiles of RNAERemer and RNAEFrassetto were significantly lower than those in the lowest tertiles (for RNAERemer: mean difference -0.084 g/cm2; P=0.007 and for RNAEFrassetto: mean difference - 0.088 g/cm2; P=0.004). Similar results were observed in a subgroup analysis of subjects with dietary calcium intake of >800 mg/day. In conclusion, a higher RNAE (i. e. more dietary acidity), which is associated with greater intake of acid-generating foods and lower intake of alkali-generating foods, may be involved in deteriorating the bone health of postmenopausal Iranian women, even in the context of adequate dietary calcium intake.

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