mOrange2, a Genetically Encoded, pH Sensitive Fluorescent Protein, is an Alternative to BCECF-AM to Measure Intracellular pH to Determine NHE3 and DRA Activity.


Journal

Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology
ISSN: 1421-9778
Titre abrégé: Cell Physiol Biochem
Pays: Germany
ID NLM: 9113221

Informations de publication

Date de publication:
26 Jan 2022
Historique:
accepted: 08 01 2022
entrez: 25 1 2022
pubmed: 26 1 2022
medline: 8 2 2022
Statut: ppublish

Résumé

NHE3 (Na The use of a genetically modified fluorescent protein, mOrange2 was explored as an intracellular pH sensor protein to measure exchange activity of NHE3 and DRA. The model used was FRT cells stably expressing NHE3 or DRA with intracellular pH measured by changes of mOrange2 fluorescence intensity. Intracellular pH was monitored using a) Isolated single clones of FRT/mOrange2/HA-NHE3 cells studied in a confocal microscope with time-lapse live cell imaging under basal conditions and when NHE3 was inhibited by exposure to forskolin and stimulated by dexamethasone, b) coverslip grown FRT/mOrange2 cells expressing NHE3 or DRA using a computerized fluorometer with a perfused cuvette with standardization of the mOrange2 absorption and emission signal using K A similar rate of intracellular alkalization by Na This study demonstrates that mOrange2 protein can be an effective alternate to BCECF-AM in measuring intracellular pH (preferred setting Ex520nm, Em 563nm) as affected by NHE3 and DRA activity, with the advantage, compared to AM ester dyes, that genetic expression can provide uniform expression of the pH sensor.

Sections du résumé

BACKGROUND/AIMS OBJECTIVE
NHE3 (Na
METHODS METHODS
The use of a genetically modified fluorescent protein, mOrange2 was explored as an intracellular pH sensor protein to measure exchange activity of NHE3 and DRA. The model used was FRT cells stably expressing NHE3 or DRA with intracellular pH measured by changes of mOrange2 fluorescence intensity. Intracellular pH was monitored using a) Isolated single clones of FRT/mOrange2/HA-NHE3 cells studied in a confocal microscope with time-lapse live cell imaging under basal conditions and when NHE3 was inhibited by exposure to forskolin and stimulated by dexamethasone, b) coverslip grown FRT/mOrange2 cells expressing NHE3 or DRA using a computerized fluorometer with a perfused cuvette with standardization of the mOrange2 absorption and emission signal using K
RESULTS RESULTS
A similar rate of intracellular alkalization by Na
CONCLUSION CONCLUSIONS
This study demonstrates that mOrange2 protein can be an effective alternate to BCECF-AM in measuring intracellular pH (preferred setting Ex520nm, Em 563nm) as affected by NHE3 and DRA activity, with the advantage, compared to AM ester dyes, that genetic expression can provide uniform expression of the pH sensor.

Identifiants

pubmed: 35076190
doi: 10.33594/000000493
doi:

Substances chimiques

Antiporters 0
Fluoresceins 0
Luminescent Proteins 0
Slc26a3 protein, rat 0
Slc9a3 protein, rat 0
Sodium-Hydrogen Exchanger 3 0
Sulfate Transporters 0
fluorescent protein 583 0
2',7'-bis(carboxyethyl)-5(6)-carboxyfluorescein 85138-49-4

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

39-49

Subventions

Organisme : NIH NIDDK
ID : RO1-DK26523, RO1-DK61765, PO1-DK64388, P30-DK89502
Pays : United States
Organisme : NIH NIAID
ID : P01-AI125181
Pays : United States
Organisme : NIH SIG
ID : 1S10OD025244
Pays : United States

Informations de copyright

© Copyright by the Author(s). Published by Cell Physiol Biochem Press.

Déclaration de conflit d'intérêts

The authors declare that no conflict of interests exists.

Auteurs

Rafiquel Sarker (R)

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Chung Ming Tse (CM)

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Ruxian Lin (R)

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

George McNamara (G)

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Varsha Singh (V)

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

Mark Donowitz (M)

Division of Gastroenterology, Department of Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD, USA, mdonowit@jhmi.edu.
Department of Physiology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA.

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Classifications MeSH