Corneal endothelial cell dysfunction: etiologies and management

Therapeutic Advances in Ophthalmology, Journal Year: 2018, Volume and Issue: 10

Published: Jan. 1, 2018

A transparent cornea is essential for the formation of a clear image on retina. The human arranged into well-organized layers, and each layer plays significant role in maintaining transparency viability tissue. endothelium has both barrier pump functions, which are important maintenance corneal clarity. Many etiologies, including Fuchs’ endothelial dystrophy, surgical trauma, congenital hereditary lead to cell dysfunction. main treatment decompensation replacement abnormal layers with normal donor Nowadays, trend perform selective keratoplasty, Descemet stripping automated keratoplasty Descemet’s membrane manage This approach several advantages over penetrating rapid recovery visual acuity, less likelihood graft rejection, better patient satisfaction. However, global limitation supply corneas becoming an increasing challenge, necessitating alternatives reduce this demand. Consequently, vitro expansion cells evolving as sustainable choice. method intended prepare that can be transferred eye. Herein, we describe etiologies manifestations We also summarize available options well recent developments management

Language: Английский

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Regulation and roles of bicarbonate transporters in cancer

Frontiers in Physiology, Journal Year: 2014, Volume and Issue: 5

Published: April 16, 2014

A unifying feature of solid tumors is a markedly altered pH profile compared to normal tissues. This reflects that tumors, despite completely different origins, often share several phenotypic properties with implications for intra- and extracellular pH. These include: metabolic shift in most cancer cells towards more acid-producing pathways, reflecting both oncogenic signaling the development hypoxia poorly perfused regions tumors; highly dense tumor microenvironment, reducing diffusive flux acid equivalents tissues; regulation expression activity pH-regulatory transport proteins cells. While some these have been well described recent years, great majority research this clinically important area has focused on proton transport, particular via Na+/H+-exchanger 1 (SLC9A1, NHE1) various H+ ATPases. We have, however, recently demonstrated at least under conditions, including vitro models HER2 positive breast cancer, measurements obtained directly freshly dissected human mammary bicarbonate transporters such as electroneutral Na+,HCO3--cotransporter (SLC4A7, NBCn1), are upregulated play central roles regulation. In review, we summarize discuss current knowledge regarding cancer.

Language: Английский

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The Concise Guide toPHARMACOLOGY2013/14: Transporters

British Journal of Pharmacology, Journal Year: 2013, Volume and Issue: 170(8), P. 1706 - 1796

Published: Dec. 1, 2013

Abstract The Concise Guide to PHARMACOLOGY 2013/14 provides concise overviews of the key properties over 2000 human drug targets with their pharmacology, plus links an open access knowledgebase and ligands ( www.guidetopharmacology.org ), which more detailed views target ligand properties. full contents can be found at http://onlinelibrary.wiley.com/doi/10.1111/bph.12444/full . Transporters are one seven major pharmacological into is divided, others being G protein‐coupled receptors, ligand‐gated ion channels, catalytic nuclear hormone receptors enzymes. These presented nomenclature guidance summary information on best available tools, alongside references suggestions for further reading. A new landscape format has easy use tables comparing related targets. It a condensed version material contemporary late 2013, in greater detail constantly updated website , superseding data previous Guides Receptors Channels. produced conjunction NC‐IUPHAR official IUPHAR classification targets, where appropriate. consolidates previously curated displayed separately IUPHAR‐DB Channels, providing permanent, citable, point‐in‐time record that will survive database updates.

Language: Английский

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Understanding the boron transport network in plants

Plant and Soil, Journal Year: 2014, Volume and Issue: 385(1-2), P. 1 - 13

Published: June 3, 2014

Language: Английский

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Impact of seawater carbonate chemistry on the calcification of marine bivalves

Biogeosciences, Journal Year: 2015, Volume and Issue: 12(14), P. 4209 - 4220

Published: July 17, 2015

Abstract. Bivalve calcification, particularly of the early larval stages, is highly sensitive to change in ocean carbonate chemistry resulting from atmospheric CO2 uptake. Earlier studies suggested that declining seawater [CO32−] and thereby lowered saturation affect shell production. However, disturbances physiological processes such as acid-base regulation by adverse pCO2 pH can calcification a secondary fashion. In order determine exact system component which growth are affected it necessary utilize more complex manipulations. As single factors, had no effects [HCO3-] only limited on growth, while strongly impacted calcification. Dissolved inorganic carbon (CT) limiting conditions led strong reductions despite high [CO32−], indicating rather than source utilized for mytilid mussels. ratio / [H+] linearly correlated with not possible differentiate between these under natural conditions. An equivalent about 80 μmol kg−1 required saturate supply bivalves. Below this threshold biomineralization rates rapidly decline. A comparison literature data available larvae juvenile mussels oysters originating habitats differing substantially respect prevailing revealed similar response curves. This suggests mechanisms sensitivity group conserved. The higher seems primarily result much relative life stages. reveal understand limit or facilitate adaptation future acidification, better their underlying genetics govern assimilation

Language: Английский

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What is pH regulation, and why do cancer cells need it?

Cancer and Metastasis Reviews, Journal Year: 2019, Volume and Issue: 38(1-2), P. 5 - 15

Published: Feb. 1, 2019

Metabolism is a continuous source of acids. To keep up with desired metabolic rate, tumors must establish an adequate means clearing their acidic end-products. This homeostatic priority achieved by various buffers, enzymes, and transporters connected through the common denominator H+ ions. Whilst this complexity proportionate to importance pH control, it problematic for developing intuition tracking route taken acids, assessing relative acid-handling proteins, predicting outcomes pharmacological inhibition or genetic alteration. Here, help simplified mathematical framework, genesis cancer regulation explained in terms obstacles efficient acid venting how these are overcome specific molecules, often associated cancer. Ultimately, regulatory apparatus (i) provide lactic permeability membranes, (ii) facilitate CO2/HCO3−/H+ diffusivity across interstitium, (iii) invest form active transport that strikes favorable balance between intracellular lactate retention under energetic constraints cell, (iv) enable necessary feedback complete loop. A more informed quantitative approach understanding mandatory identifying vulnerabilities, which could be exploited as therapeutic targets.

Language: Английский

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A look at the smelly side of physiology: transport of short chain fatty acids

Pflügers Archiv - European Journal of Physiology, Journal Year: 2018, Volume and Issue: 470(4), P. 571 - 598

Published: Jan. 6, 2018

Language: Английский

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Loss-of-activity-mutation in the cardiac chloride-bicarbonate exchanger AE3 causes short QT syndrome

Nature Communications, Journal Year: 2017, Volume and Issue: 8(1)

Published: Nov. 16, 2017

Abstract Patients with short QT syndrome (SQTS) may present syncope, ventricular fibrillation or sudden cardiac death. Six SQTS susceptibility genes, encoding cation channels, explain <25% of cases. Here we identify a missense mutation in the anion exchanger (AE3)-encoding SLC4A3 gene two unrelated families SQTS. The causes reduced surface expression AE3 and membrane bicarbonate transport. Slc4a3 knockdown zebrafish increased pH i , QTc, systolic duration, which is rescued by wildtype but not mutated . Mechanistic analyses suggest that an increase decrease [Cl − ] shortened action potential duration. However, other mechanisms also play role. Altered transport represents mechanism for development arrhythmia provide new therapeutic possibilities.

Language: Английский

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The Na⁺/HCO₃⁻Co-Transporter SLC4A4 Plays a Role in Growth and Migration of Colon and Breast Cancer Cells

Journal of Cellular Physiology, Journal Year: 2015, Volume and Issue: 230(8), P. 1954 - 1963

Published: Jan. 22, 2015

The hypoxic and acidic tumor environment necessitates intracellular pH (pHi) regulation for progression. Carbonic anhydrase IX (CA IX; hypoxia-induced) is known to facilitate CO2 export generate HCO3− in the extracellular space. It has been proposed that re-captured by cell maintain an alkaline pHi. A diverse range of transporters, coupled with a lack clear over-expression cancers have limited molecular identification this cellular process. Here, we report hypoxia induces Na+/HCO3− co-transporter (NBCe1) SLC4A4 mRNA expression exclusively LS174 colon adenocarcinoma line HIF1α dependent manner. pHi recovery observations revealed predominant use NBC mechanism suggesting reversal Cl−/HCO3− exchanger not utilized regulation. Knockdown via shRNA reduced proliferation increased mortality during external acidosis spheroid growth. from was partially knockdown SLC4A4. In MDA-MB-231 breast cancer cells expressing high levels compared cells, had strong impact on proliferation, migration, invasion. also altered other proteins including CA IX. Furthermore cells. Combined our results indicate contributes transport phenotype. This study complements on-going characterization re-uptake future strategies targeting these potentially important drug targets. J. Cell. Physiol. 230: 1954–1963, 2015. © 2015 Wiley Periodicals, Inc.

Language: Английский

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Transport and Use of Bicarbonate in Plants: Current Knowledge and Challenges Ahead

International Journal of Molecular Sciences, Journal Year: 2018, Volume and Issue: 19(5), P. 1352 - 1352

Published: May 3, 2018

Bicarbonate plays a fundamental role in the cell pH status all organisms. In autotrophs, HCO3− may further contribute to carbon concentration mechanisms (CCM). This is especially relevant CO2-poor habitats of cyanobacteria, aquatic microalgae, and macrophytes. Photosynthesis terrestrial plants can also benefit from CCM as evidenced by evolution C4 Crassulacean Acid Metabolism (CAM). The presence organisms leads more questions regarding uptake membrane transport these different biological systems. review aims provide an overview metabolic processes related macroalgae, seagrasses, plants. cyanobacteria human cells much better documented included for comparison. We comment on roles focusing diversity functions carbonic anhydrases PEP carboxylases well signaling CO2/HCO3− stomatal guard cells. Plant responses excess soil briefly addressed. conclusion, there are still considerable gaps our knowledge that hamper development breeding strategies both efficient tolerance crop

Language: Английский

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