Activation of rat hepatic stellate cells leads to loss of glutathione s- transferases and their enzymatic activity against products of oxidative stress

Richard Whalen, Don C. Rockey, Scott L. Friedman, Thomas D Boyer

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

Oxidative stress, mediated partly by lipid peroxidation products, may lead to increased collagen synthesis by hepatic stellate cells (HSC). Stellate cells are protected from oxidative stress by enzymes of detoxication such as the glutathione S-transferases (GSTs), which form glutathione conjugates with lipid peroxidation products (e.g., 4-hydroxy-2-nonenal [HNE]). To better understand the role of GSTs in stellate cell biology, we examined the expression and enzymatic activity of GSTs in normal and activated (both culture- and in vivo-activated) stellate cells. Normal stellate cells contained numerous isoforms of GST including those that detoxify HNE. High levels of enzymatic activity toward 1-chloro-2,4- dinitrobenzene (CDNB) and HNE were present in normal stellate cells and were similar to levels present in whole liver. Following activation by growth in culture, the expression of several GSTs (rGSTA1/A2, A3, and M1) was lost. Also, enzymatic activities toward CDNB and HNE fell ~90%. However, expression of rGSTP1 was maintained. A similar loss of rGSTA1/A2, A3, and M1 with persistent expression of rGSTP1 was present after activation in vivo. Furthermore, we identified 2 subpopulations of activated stellate cells with different GST phenotypes from injured livers. In summary, activated stellate cells lose most forms of GST and associated enzymatic activities that are present in normal stellate cells. The findings raise the possibility that activated stellate cells have less ability to detoxify lipid peroxidation products and may be susceptible to oxidative stress. Additionally, we propose that the phenotypic change in GSTs is a sensitive marker of stellate cell activation.

Original languageEnglish (US)
Pages (from-to)927-933
Number of pages7
JournalHepatology
Volume30
Issue number4
DOIs
StatePublished - 1999
Externally publishedYes

Fingerprint

Hepatic Stellate Cells
Glutathione Transferase
Oxidative Stress
Lipid Peroxidation
Liver
varespladib methyl
Glutathione
Cell Biology
Protein Isoforms
Collagen
Phenotype

ASJC Scopus subject areas

  • Hepatology

Cite this

Activation of rat hepatic stellate cells leads to loss of glutathione s- transferases and their enzymatic activity against products of oxidative stress. / Whalen, Richard; Rockey, Don C.; Friedman, Scott L.; Boyer, Thomas D.

In: Hepatology, Vol. 30, No. 4, 1999, p. 927-933.

Research output: Contribution to journalArticle

@article{335a300c3b0646838a71d2e0d00b3c3e,
title = "Activation of rat hepatic stellate cells leads to loss of glutathione s- transferases and their enzymatic activity against products of oxidative stress",
abstract = "Oxidative stress, mediated partly by lipid peroxidation products, may lead to increased collagen synthesis by hepatic stellate cells (HSC). Stellate cells are protected from oxidative stress by enzymes of detoxication such as the glutathione S-transferases (GSTs), which form glutathione conjugates with lipid peroxidation products (e.g., 4-hydroxy-2-nonenal [HNE]). To better understand the role of GSTs in stellate cell biology, we examined the expression and enzymatic activity of GSTs in normal and activated (both culture- and in vivo-activated) stellate cells. Normal stellate cells contained numerous isoforms of GST including those that detoxify HNE. High levels of enzymatic activity toward 1-chloro-2,4- dinitrobenzene (CDNB) and HNE were present in normal stellate cells and were similar to levels present in whole liver. Following activation by growth in culture, the expression of several GSTs (rGSTA1/A2, A3, and M1) was lost. Also, enzymatic activities toward CDNB and HNE fell ~90{\%}. However, expression of rGSTP1 was maintained. A similar loss of rGSTA1/A2, A3, and M1 with persistent expression of rGSTP1 was present after activation in vivo. Furthermore, we identified 2 subpopulations of activated stellate cells with different GST phenotypes from injured livers. In summary, activated stellate cells lose most forms of GST and associated enzymatic activities that are present in normal stellate cells. The findings raise the possibility that activated stellate cells have less ability to detoxify lipid peroxidation products and may be susceptible to oxidative stress. Additionally, we propose that the phenotypic change in GSTs is a sensitive marker of stellate cell activation.",
author = "Richard Whalen and Rockey, {Don C.} and Friedman, {Scott L.} and Boyer, {Thomas D}",
year = "1999",
doi = "10.1002/hep.510300404",
language = "English (US)",
volume = "30",
pages = "927--933",
journal = "Hepatology",
issn = "0270-9139",
publisher = "John Wiley and Sons Ltd",
number = "4",

}

TY - JOUR

T1 - Activation of rat hepatic stellate cells leads to loss of glutathione s- transferases and their enzymatic activity against products of oxidative stress

AU - Whalen, Richard

AU - Rockey, Don C.

AU - Friedman, Scott L.

AU - Boyer, Thomas D

PY - 1999

Y1 - 1999

N2 - Oxidative stress, mediated partly by lipid peroxidation products, may lead to increased collagen synthesis by hepatic stellate cells (HSC). Stellate cells are protected from oxidative stress by enzymes of detoxication such as the glutathione S-transferases (GSTs), which form glutathione conjugates with lipid peroxidation products (e.g., 4-hydroxy-2-nonenal [HNE]). To better understand the role of GSTs in stellate cell biology, we examined the expression and enzymatic activity of GSTs in normal and activated (both culture- and in vivo-activated) stellate cells. Normal stellate cells contained numerous isoforms of GST including those that detoxify HNE. High levels of enzymatic activity toward 1-chloro-2,4- dinitrobenzene (CDNB) and HNE were present in normal stellate cells and were similar to levels present in whole liver. Following activation by growth in culture, the expression of several GSTs (rGSTA1/A2, A3, and M1) was lost. Also, enzymatic activities toward CDNB and HNE fell ~90%. However, expression of rGSTP1 was maintained. A similar loss of rGSTA1/A2, A3, and M1 with persistent expression of rGSTP1 was present after activation in vivo. Furthermore, we identified 2 subpopulations of activated stellate cells with different GST phenotypes from injured livers. In summary, activated stellate cells lose most forms of GST and associated enzymatic activities that are present in normal stellate cells. The findings raise the possibility that activated stellate cells have less ability to detoxify lipid peroxidation products and may be susceptible to oxidative stress. Additionally, we propose that the phenotypic change in GSTs is a sensitive marker of stellate cell activation.

AB - Oxidative stress, mediated partly by lipid peroxidation products, may lead to increased collagen synthesis by hepatic stellate cells (HSC). Stellate cells are protected from oxidative stress by enzymes of detoxication such as the glutathione S-transferases (GSTs), which form glutathione conjugates with lipid peroxidation products (e.g., 4-hydroxy-2-nonenal [HNE]). To better understand the role of GSTs in stellate cell biology, we examined the expression and enzymatic activity of GSTs in normal and activated (both culture- and in vivo-activated) stellate cells. Normal stellate cells contained numerous isoforms of GST including those that detoxify HNE. High levels of enzymatic activity toward 1-chloro-2,4- dinitrobenzene (CDNB) and HNE were present in normal stellate cells and were similar to levels present in whole liver. Following activation by growth in culture, the expression of several GSTs (rGSTA1/A2, A3, and M1) was lost. Also, enzymatic activities toward CDNB and HNE fell ~90%. However, expression of rGSTP1 was maintained. A similar loss of rGSTA1/A2, A3, and M1 with persistent expression of rGSTP1 was present after activation in vivo. Furthermore, we identified 2 subpopulations of activated stellate cells with different GST phenotypes from injured livers. In summary, activated stellate cells lose most forms of GST and associated enzymatic activities that are present in normal stellate cells. The findings raise the possibility that activated stellate cells have less ability to detoxify lipid peroxidation products and may be susceptible to oxidative stress. Additionally, we propose that the phenotypic change in GSTs is a sensitive marker of stellate cell activation.

UR - http://www.scopus.com/inward/record.url?scp=0032836925&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032836925&partnerID=8YFLogxK

U2 - 10.1002/hep.510300404

DO - 10.1002/hep.510300404

M3 - Article

C2 - 10498644

AN - SCOPUS:0032836925

VL - 30

SP - 927

EP - 933

JO - Hepatology

JF - Hepatology

SN - 0270-9139

IS - 4

ER -