Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes › Research Explorer (2023)

Standard

Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes. / Reiniers, Megan J.; de Haan, Lianne R.; Reeskamp, Laurens F. et al.

Methods in Molecular Biology. Vol. 2451 Humana Press Inc., 2022. p. 721-747 (Methods in Molecular Biology; Vol. 2451).

Research output: Chapter in Book/Report/Conference proceedingChapterAcademicpeer-review

Harvard

Reiniers, MJ, de Haan, LR, Reeskamp, LF, Broekgaarden, M, Hoekstra, R, van Golen, RF 2022, Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes. in Methods in Molecular Biology. vol. 2451, Methods in Molecular Biology, vol. 2451, Humana Press Inc., pp. 721-747. https://doi.org/10.1007/978-1-0716-2099-1_39

APA

Reiniers, M. J., de Haan, L. R., Reeskamp, L. F., Broekgaarden, M., Hoekstra, R., van Golen, R. F. (2022). Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes. In Methods in Molecular Biology (Vol. 2451, pp. 721-747). (Methods in Molecular Biology; Vol. 2451). Humana Press Inc.. https://doi.org/10.1007/978-1-0716-2099-1_39

Vancouver

Reiniers MJ, de Haan LR, Reeskamp LF, Broekgaarden M, Hoekstra R, van Golen RF et al. Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes. In Methods in Molecular Biology. Vol. 2451. Humana Press Inc. 2022. p. 721-747. (Methods in Molecular Biology). doi: 10.1007/978-1-0716-2099-1_39

Author

Reiniers, Megan J. ; de Haan, Lianne R. ; Reeskamp, Laurens F. et al. / Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes. Methods in Molecular Biology. Vol. 2451 Humana Press Inc., 2022. pp. 721-747 (Methods in Molecular Biology).

BibTeX

@inbook{638e9f4bf90b461f9f6be586828c9a67,

title = "Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes",

abstract = "Oxidative stress is a state that arises when the production of reactive transients overwhelms the cell{\textquoteright}s capacity to neutralize the oxidants and radicals. This state often coincides with the pathogenesis and perpetuation of numerous chronic diseases. On the other hand, medical interventions such as radiation therapy and photodynamic therapy generate radicals to selectively damage and kill diseased tissue. As a result, the qualification and quantification of oxidative stress are of great interest to those studying disease mechanisms as well as therapeutic interventions. 2′,7′-Dichlorodihydrofluorescein-diacetate (DCFH2-DA) is one of the most widely used fluorogenic probes for the detection of reactive transients. The nonfluorescent DCFH2-DA crosses the plasma membrane and is deacetylated by cytosolic esterases to 2′,7′-dichlorodihydrofluorescein (DCFH2). The nonfluorescent DCFH2 is subsequently oxidized by reactive transients to form the fluorescent 2′,7′-dichlorofluorescein (DCF). The use of DCFH2-DA in hepatocyte-derived cell lines is more challenging because of membrane transport proteins that interfere with probe uptake and retention, among several other reasons. Cancer cells share some of the physiological and biochemical features with hepatocytes, so probe-related technical issues are applicable to cultured malignant cells as well. This study therefore analyzed the in vitro properties of DCFH2-DA in cultured human hepatocytes (HepG2 cells and differentiated and undifferentiated HepaRG cells) to identify methodological and technical features that could impair proper data analysis and interpretation. The main issues that were found and should therefore be accounted for in experimental design include the following: (1) both DCFH2-DA and DCF are taken up rapidly, (2) DCF is poorly retained in the cytosol and exits the cell, (3) the rate of DCFH2 oxidation is cell type-specific, (4) DCF fluorescence intensity is pH-dependent at pH < 7, and (5) the stability of DCFH2-DA in cell culture medium relies on medium composition. Based on the findings, the conditions for the use of DCFH2-DA in hepatocyte cell lines were optimized. Finally, the optimized protocol was reduced to practice and DCFH2-DA was applied to visualize and quantify oxidative stress in real time in HepG2 cells subjected to anoxia/reoxygenation as a source of reactive transients.",

keywords = "2′,7′-Dichlorodihydrofluorescein-diacetate, 2′,7′-Dichlorofluorescein, Cellular uptake and efflux, Fluorogenic redox probe, Hepatocytes, Oxidative and nitrosative stress",

author = "Reiniers, {Megan J.} and {de Haan}, {Lianne R.} and Reeskamp, {Laurens F.} and Mans Broekgaarden and Ruurdtje Hoekstra and {van Golen}, {Rowan F.} and Michal Heger",

note = "Publisher Copyright: {\textcopyright} 2022, Springer Science+Business Media, LLC, part of Springer Nature.",

year = "2022",

doi = "10.1007/978-1-0716-2099-1_39",

language = "English",

volume = "2451",

series = "Methods in Molecular Biology",

publisher = "Humana Press Inc.",

pages = "721--747",

booktitle = "Methods in Molecular Biology",

}

RIS

TY - CHAP

T1 - Optimal Use of 2′,7′-Dichlorofluorescein Diacetate in Cultured Hepatocytes

AU - Reiniers, Megan J.

AU - de Haan, Lianne R.

AU - Reeskamp, Laurens F.

AU - Broekgaarden, Mans

AU - Hoekstra, Ruurdtje

AU - van Golen, Rowan F.

AU - Heger, Michal

N1 - Publisher Copyright:© 2022, Springer Science+Business Media, LLC, part of Springer Nature.

PY - 2022

Y1 - 2022

N2 - Oxidative stress is a state that arises when the production of reactive transients overwhelms the cell’s capacity to neutralize the oxidants and radicals. This state often coincides with the pathogenesis and perpetuation of numerous chronic diseases. On the other hand, medical interventions such as radiation therapy and photodynamic therapy generate radicals to selectively damage and kill diseased tissue. As a result, the qualification and quantification of oxidative stress are of great interest to those studying disease mechanisms as well as therapeutic interventions. 2′,7′-Dichlorodihydrofluorescein-diacetate (DCFH2-DA) is one of the most widely used fluorogenic probes for the detection of reactive transients. The nonfluorescent DCFH2-DA crosses the plasma membrane and is deacetylated by cytosolic esterases to 2′,7′-dichlorodihydrofluorescein (DCFH2). The nonfluorescent DCFH2 is subsequently oxidized by reactive transients to form the fluorescent 2′,7′-dichlorofluorescein (DCF). The use of DCFH2-DA in hepatocyte-derived cell lines is more challenging because of membrane transport proteins that interfere with probe uptake and retention, among several other reasons. Cancer cells share some of the physiological and biochemical features with hepatocytes, so probe-related technical issues are applicable to cultured malignant cells as well. This study therefore analyzed the in vitro properties of DCFH2-DA in cultured human hepatocytes (HepG2 cells and differentiated and undifferentiated HepaRG cells) to identify methodological and technical features that could impair proper data analysis and interpretation. The main issues that were found and should therefore be accounted for in experimental design include the following: (1) both DCFH2-DA and DCF are taken up rapidly, (2) DCF is poorly retained in the cytosol and exits the cell, (3) the rate of DCFH2 oxidation is cell type-specific, (4) DCF fluorescence intensity is pH-dependent at pH < 7, and (5) the stability of DCFH2-DA in cell culture medium relies on medium composition. Based on the findings, the conditions for the use of DCFH2-DA in hepatocyte cell lines were optimized. Finally, the optimized protocol was reduced to practice and DCFH2-DA was applied to visualize and quantify oxidative stress in real time in HepG2 cells subjected to anoxia/reoxygenation as a source of reactive transients.

AB - Oxidative stress is a state that arises when the production of reactive transients overwhelms the cell’s capacity to neutralize the oxidants and radicals. This state often coincides with the pathogenesis and perpetuation of numerous chronic diseases. On the other hand, medical interventions such as radiation therapy and photodynamic therapy generate radicals to selectively damage and kill diseased tissue. As a result, the qualification and quantification of oxidative stress are of great interest to those studying disease mechanisms as well as therapeutic interventions. 2′,7′-Dichlorodihydrofluorescein-diacetate (DCFH2-DA) is one of the most widely used fluorogenic probes for the detection of reactive transients. The nonfluorescent DCFH2-DA crosses the plasma membrane and is deacetylated by cytosolic esterases to 2′,7′-dichlorodihydrofluorescein (DCFH2). The nonfluorescent DCFH2 is subsequently oxidized by reactive transients to form the fluorescent 2′,7′-dichlorofluorescein (DCF). The use of DCFH2-DA in hepatocyte-derived cell lines is more challenging because of membrane transport proteins that interfere with probe uptake and retention, among several other reasons. Cancer cells share some of the physiological and biochemical features with hepatocytes, so probe-related technical issues are applicable to cultured malignant cells as well. This study therefore analyzed the in vitro properties of DCFH2-DA in cultured human hepatocytes (HepG2 cells and differentiated and undifferentiated HepaRG cells) to identify methodological and technical features that could impair proper data analysis and interpretation. The main issues that were found and should therefore be accounted for in experimental design include the following: (1) both DCFH2-DA and DCF are taken up rapidly, (2) DCF is poorly retained in the cytosol and exits the cell, (3) the rate of DCFH2 oxidation is cell type-specific, (4) DCF fluorescence intensity is pH-dependent at pH < 7, and (5) the stability of DCFH2-DA in cell culture medium relies on medium composition. Based on the findings, the conditions for the use of DCFH2-DA in hepatocyte cell lines were optimized. Finally, the optimized protocol was reduced to practice and DCFH2-DA was applied to visualize and quantify oxidative stress in real time in HepG2 cells subjected to anoxia/reoxygenation as a source of reactive transients.

KW - 2′,7′-Dichlorodihydrofluorescein-diacetate

KW - 2′,7′-Dichlorofluorescein

KW - Cellular uptake and efflux

KW - Fluorogenic redox probe

KW - Hepatocytes

KW - Oxidative and nitrosative stress

UR - http://www.scopus.com/inward/record.url?scp=85129572313&partnerID=8YFLogxK

U2 - 10.1007/978-1-0716-2099-1_39

DO - 10.1007/978-1-0716-2099-1_39

M3 - Chapter

C2 - 35505044

VL - 2451

T3 - Methods in Molecular Biology

SP - 721

EP - 747

BT - Methods in Molecular Biology

PB - Humana Press Inc.

ER -

Top Articles
Latest Posts
Article information

Author: Delena Feil

Last Updated: 04/06/2023

Views: 6112

Rating: 4.4 / 5 (65 voted)

Reviews: 80% of readers found this page helpful

Author information

Name: Delena Feil

Birthday: 1998-08-29

Address: 747 Lubowitz Run, Sidmouth, HI 90646-5543

Phone: +99513241752844

Job: Design Supervisor

Hobby: Digital arts, Lacemaking, Air sports, Running, Scouting, Shooting, Puzzles

Introduction: My name is Delena Feil, I am a clean, splendid, calm, fancy, jolly, bright, faithful person who loves writing and wants to share my knowledge and understanding with you.