Evidence map›Paper›PMID 21896839›Full record

ArticleInvestigative ophthalmology & visual science2011

Bicarbonate, NBCe1, NHE, and carbonic anhydrase activity enhance lactate-H+ transport in bovine corneal endothelium.

Tracy T Nguyen, Joseph A Bonanno

Open access · bronzeAbstract read
In one paragraph

Article in Investigative ophthalmology & visual science, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
1.7field-weighted citation impact, top 16% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

24 citing papers in PubMed, 32 citations in OpenAlex.

  1. Trial
  2. Review
  3. Biomolecules · 2025
    Review
  4. Squishy matters - Corneal mechanobiology in health and disease.Progress in retinal and eye research · 2024
    Review
  5. Carbonic anhydrase, its inhibitors and vascular function.Frontiers in molecular biosciences · 2024
    Review
  6. Article
  7. Article
  8. Diseases of the corneal endothelium.Experimental eye research · 2021
    Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. CD147 required for corneal endothelial lactate transport.Investigative ophthalmology & visual science · 2014
    Article
  17. Cornea and ocular surface disease: application of cutting-edge optometric research.Optometry and vision science : official publication of the American Academy of Optometry · 2014
    Review
  18. Article
  19. Article
  20. Ion transport function of SLC4A11 in corneal endothelium.Investigative ophthalmology & visual science · 2013
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

2 authors at 1 institution in 1 country.

Tracy T NguyenSchool of Optometry, Indiana University, Bloomington, Indiana 47405, USA.
Joseph A Bonanno
Indiana University Bloomington · US

Funding

REGULATION OF PHI AND FLUID FLUX IN CORNEAL ENDOTHELIUMR01EY008834 · NEI · UNIVERSITY OF CALIFORNIA BERKELEY · PI BONANNO, JOSEPH AURELIO · 1991 to 2020
$7.8M
Core Support for Vision Research at Indiana UniversityP30EY019008 · NEI · TRUSTEES OF INDIANA UNIVERSITY · PI BURNS, STEPHEN A · 2009 to 2013
$2.1M
Visual Optics and CorneaK12EY015504 · NEI · TRUSTEES OF INDIANA UNIVERSITY · PI SONI, P SARITA · 2004 to 2008
$1.3M
Lactic acid transport across the corneal endotheliumK08EY019537 · NEI · TRUSTEES OF INDIANA UNIVERSITY · PI NGUYEN, TRACY THUY · 2009 to 2013
$666k
NEI NIH HHS K08 EY019537NEI NIH HHS K08EY019537NEI NIH HHS K12 EY015504NEI NIH HHS K12EY015504NEI NIH HHS P30 EY019008NEI NIH HHS P30EY019008NEI NIH HHS R01 EY008834NEI NIH HHS R01EY08834
6 · The paper itself

Abstract

purposeTo identify and localize the monocarboxylate transporters (MCTs) expressed in bovine corneal endothelial cells (BCEC) and to test the hypothesis that buffering contributed by HCO(3)(-), sodium bicarbonate cotransporter (NBCe1), sodium hydrogen exchanger (NHE), and carbonic anhydrase (CA) activity facilitates lactate flux.

methodsMCT1-4 expression was screened by RT-PCR, Western blot analysis, and immunofluorescence. Endogenous lactate efflux and/or pH(i) were measured in BCEC in HCO(3)(-)-free or HCO(3)(-)-rich Ringer, with and without niflumic acid (MCT inhibitor), acetazolamide (ACTZ, a CA inhibitor), 5-(N-Ethyl-N-isopropyl)amiloride (EIPA) (Na(+)/H(+) exchange blocker), disodium 4,4'-diisothiocyanatostilbene-2,2'-disulfonate (DIDS; anion transport inhibitor), or with NBCe1-specific small interfering (si) RNA-treated cells.

resultsMCT1, 2, and 4 are expressed in BCEC. MCT1 was localized to the lateral membrane, MCT2 was lateral and apical, while MCT4 was apical. pH(i) measurements showed significant lactate-induced cell acidification (LIA) in response to 20-second pulses of lactate. Incubation with niflumic acid significantly reduced the rate of pHi change (dpH(i)/dt) and lactate-induced cell acidification. EIPA inhibited alkalinization after lactate removal. Lactate-dependent proton flux was significantly greater in the presence of HCO(3)(-) but was reduced by ACTZ. Efflux of endogenously produced lactate was significantly faster in the presence of HCO(3)(-), was greater on the apical surface, was reduced on the apical side by ACTZ, as well as on the apical and basolateral side by NBCe1-specific siRNA, DIDS, or EIPA.

conclusionsMCT1, 2, and 4 are expressed in BCEC on both the apical and basolateral membrane (BL) surfaces consistent with niflumic acid-sensitive lactate-H(+) transport. Lactate dependent proton flux can activate Na(+)/H(+) exchange and be facilitated by maximizing intracellular buffering capacity through the presence of HCO(3)(-), HCO(3)(-) transport, NHE and CA activity.

Indexed as

4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmilorideAnimalsBicarbonatesBlotting, WesternCarbonic Anhydrase InhibitorsCarbonic AnhydrasesCattleCells, CulturedEndothelium, CornealFluorescent Antibody Technique, IndirectHydrogen-Ion ConcentrationLactic AcidMonocarboxylic Acid TransportersNiflumic AcidReal-Time Polymerase Chain Reaction4,4'-Diisothiocyanostilbene-2,2'-Disulfonic AcidAmilorideBicarbonatesCarbonic Anhydrase InhibitorsCarbonic AnhydrasesethylisopropylamilorideLactic AcidMonocarboxylic Acid TransportersNiflumic AcidSodium-Bicarbonate SymportersSodium-Hydrogen Exchangers

Identifiers

PMID21896839
PMCPMC3208007
OpenAlexW2042715218

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.