Roles of reactive oxygen species, NF-κB, and peroxiredoxins in glycochenodeoxycholic acid-induced rat hepatocytes death

San Hui Chu, Jihee Lee-Kang, Kweon Haeng Lee, Kyungeun Lee

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

The aim of this study was to determine the roles of reactive oxygen species (ROS), NF-κB and antioxidants in glycochenodeoxycholic acid (GCDC, 0-400 μmol/l, 0.5-3 h)-induced hepatocytes death. The differential uptake of ethidium bromide and acridine orange revealed that apoptotic death occurred dose-dependently in GCDC-treated hepatocytes whereas necrotic death was prominent especially at higher GCDC concentrations (≥200 μmol/l). ROS generation measured fluorometrically either by a confocal laser microscope or by a microplate fluorescence reader was increased dose-dependently. The dose-dependent NF-κB activation with the significant IκB-α decrease preceded both hepatocyte cell death and the alteration of antioxidant enzymes. The Cu/Zn-SOD level among several antioxidants, we checked, remained unchanged. In contrast, the catalase level and its enzymatic activity were markedly decreased only at 400 μmol/l. The Prx I and Prx II, newly defined antioxidant enzymes reducing H2O2 levels were decreased at the 200 and 400 μmol/l. These observations point to ROS generation in the GCDC-treated hepatocyte as the proximate event that triggers NF-κB activation, IκB-α proteolysis, Prx depletion, and finally cell death. And oxidative stress may be more related to necrotic cell death in GCDC-treated hepatocytes.

Original languageEnglish
Pages (from-to)12-19
Number of pages8
JournalPharmacology
Volume69
Issue number1
DOIs
Publication statusPublished - 2003 Aug 11

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Glycochenodeoxycholic Acid
Peroxiredoxins
Hepatocytes
Reactive Oxygen Species
Antioxidants
Cell Death
Acridine Orange
Ethidium
Enzymes
Catalase
Proteolysis
Oxidative Stress
Lasers
Fluorescence

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Chu, San Hui ; Lee-Kang, Jihee ; Lee, Kweon Haeng ; Lee, Kyungeun. / Roles of reactive oxygen species, NF-κB, and peroxiredoxins in glycochenodeoxycholic acid-induced rat hepatocytes death. In: Pharmacology. 2003 ; Vol. 69, No. 1. pp. 12-19.
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Roles of reactive oxygen species, NF-κB, and peroxiredoxins in glycochenodeoxycholic acid-induced rat hepatocytes death. / Chu, San Hui; Lee-Kang, Jihee; Lee, Kweon Haeng; Lee, Kyungeun.

In: Pharmacology, Vol. 69, No. 1, 11.08.2003, p. 12-19.

Research output: Contribution to journalArticle

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