Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities

Emiko L. Hatcher, Yan Chen, Yujian Kang

Research output: Contribution to journalArticle

81 Citations (Scopus)

Abstract

Glutathione has been implicated to function in cytoprotection against cadmium toxicity. The mechanism by which glutathione plays this role has not been well understood. Because glutathione is an important antioxidant and several studies have shown that cadmium induces oxidative stress, this study was undertaken to determine whether development of cadmium resistance is linked to enhanced antioxidant activities. A cadmium-resistant subpopulation of human lung carcinoma A549 cells, which was developed by repeatedly exposing the cells to step-wise increased cadmium concentrations, was compared to a cadmium-sensitive one. The acquired cadmium resistance resulted from neither decreased cadmium uptake nor enhanced cellular metallothionein synthesis. Glutathione content, however, was markedly elevated in the cadmium-resistant cells. In contrast, the activities of the glutathione redox cycle related enzymes, glutathione peroxidase and reductase, were unchanged. Two other antioxidant enzymes, superoxide dismutase and catalase, were also not altered. The results suggest that the development of cadmium resistance in A549 cells unlikely results from enhanced antioxidant enzyme activities, although it is associated with elevated cellular glutathione levels. In addition, measurement of the mRNA and DNA levels for γ-glutamyleysteine synthetase, the rate-limiting enzyme for glutathione biosynthesis, revealed that enhanced expression of the enzyme but not gene amplification is likely responsible for the elevation of cellular glutathione levels.

Original languageEnglish (US)
Pages (from-to)805-812
Number of pages8
JournalFree Radical Biology and Medicine
Volume19
Issue number6
DOIs
StatePublished - Jan 1 1995
Externally publishedYes

Fingerprint

Cadmium
Glutathione
Antioxidants
Enzymes
A549 Cells
Oxidative stress
Cytoprotection
Glutathione Reductase
Metallothionein
Gene Amplification
Biosynthesis
Enzyme activity
Ligases
Glutathione Peroxidase
Catalase
Superoxide Dismutase
Oxidation-Reduction
Toxicity
Oxidative Stress
Carcinoma

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physiology (medical)

Cite this

Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities. / Hatcher, Emiko L.; Chen, Yan; Kang, Yujian.

In: Free Radical Biology and Medicine, Vol. 19, No. 6, 01.01.1995, p. 805-812.

Research output: Contribution to journalArticle

@article{260f9b1f555a454bb954b344ae69713a,
title = "Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities",
abstract = "Glutathione has been implicated to function in cytoprotection against cadmium toxicity. The mechanism by which glutathione plays this role has not been well understood. Because glutathione is an important antioxidant and several studies have shown that cadmium induces oxidative stress, this study was undertaken to determine whether development of cadmium resistance is linked to enhanced antioxidant activities. A cadmium-resistant subpopulation of human lung carcinoma A549 cells, which was developed by repeatedly exposing the cells to step-wise increased cadmium concentrations, was compared to a cadmium-sensitive one. The acquired cadmium resistance resulted from neither decreased cadmium uptake nor enhanced cellular metallothionein synthesis. Glutathione content, however, was markedly elevated in the cadmium-resistant cells. In contrast, the activities of the glutathione redox cycle related enzymes, glutathione peroxidase and reductase, were unchanged. Two other antioxidant enzymes, superoxide dismutase and catalase, were also not altered. The results suggest that the development of cadmium resistance in A549 cells unlikely results from enhanced antioxidant enzyme activities, although it is associated with elevated cellular glutathione levels. In addition, measurement of the mRNA and DNA levels for γ-glutamyleysteine synthetase, the rate-limiting enzyme for glutathione biosynthesis, revealed that enhanced expression of the enzyme but not gene amplification is likely responsible for the elevation of cellular glutathione levels.",
author = "Hatcher, {Emiko L.} and Yan Chen and Yujian Kang",
year = "1995",
month = "1",
day = "1",
doi = "10.1016/0891-5849(95)00099-J",
language = "English (US)",
volume = "19",
pages = "805--812",
journal = "Free Radical Biology and Medicine",
issn = "0891-5849",
publisher = "Elsevier Inc.",
number = "6",

}

TY - JOUR

T1 - Cadmium resistance in A549 cells correlates with elevated glutathione content but not antioxidant enzymatic activities

AU - Hatcher, Emiko L.

AU - Chen, Yan

AU - Kang, Yujian

PY - 1995/1/1

Y1 - 1995/1/1

N2 - Glutathione has been implicated to function in cytoprotection against cadmium toxicity. The mechanism by which glutathione plays this role has not been well understood. Because glutathione is an important antioxidant and several studies have shown that cadmium induces oxidative stress, this study was undertaken to determine whether development of cadmium resistance is linked to enhanced antioxidant activities. A cadmium-resistant subpopulation of human lung carcinoma A549 cells, which was developed by repeatedly exposing the cells to step-wise increased cadmium concentrations, was compared to a cadmium-sensitive one. The acquired cadmium resistance resulted from neither decreased cadmium uptake nor enhanced cellular metallothionein synthesis. Glutathione content, however, was markedly elevated in the cadmium-resistant cells. In contrast, the activities of the glutathione redox cycle related enzymes, glutathione peroxidase and reductase, were unchanged. Two other antioxidant enzymes, superoxide dismutase and catalase, were also not altered. The results suggest that the development of cadmium resistance in A549 cells unlikely results from enhanced antioxidant enzyme activities, although it is associated with elevated cellular glutathione levels. In addition, measurement of the mRNA and DNA levels for γ-glutamyleysteine synthetase, the rate-limiting enzyme for glutathione biosynthesis, revealed that enhanced expression of the enzyme but not gene amplification is likely responsible for the elevation of cellular glutathione levels.

AB - Glutathione has been implicated to function in cytoprotection against cadmium toxicity. The mechanism by which glutathione plays this role has not been well understood. Because glutathione is an important antioxidant and several studies have shown that cadmium induces oxidative stress, this study was undertaken to determine whether development of cadmium resistance is linked to enhanced antioxidant activities. A cadmium-resistant subpopulation of human lung carcinoma A549 cells, which was developed by repeatedly exposing the cells to step-wise increased cadmium concentrations, was compared to a cadmium-sensitive one. The acquired cadmium resistance resulted from neither decreased cadmium uptake nor enhanced cellular metallothionein synthesis. Glutathione content, however, was markedly elevated in the cadmium-resistant cells. In contrast, the activities of the glutathione redox cycle related enzymes, glutathione peroxidase and reductase, were unchanged. Two other antioxidant enzymes, superoxide dismutase and catalase, were also not altered. The results suggest that the development of cadmium resistance in A549 cells unlikely results from enhanced antioxidant enzyme activities, although it is associated with elevated cellular glutathione levels. In addition, measurement of the mRNA and DNA levels for γ-glutamyleysteine synthetase, the rate-limiting enzyme for glutathione biosynthesis, revealed that enhanced expression of the enzyme but not gene amplification is likely responsible for the elevation of cellular glutathione levels.

UR - http://www.scopus.com/inward/record.url?scp=0028785643&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0028785643&partnerID=8YFLogxK

U2 - 10.1016/0891-5849(95)00099-J

DO - 10.1016/0891-5849(95)00099-J

M3 - Article

VL - 19

SP - 805

EP - 812

JO - Free Radical Biology and Medicine

JF - Free Radical Biology and Medicine

SN - 0891-5849

IS - 6

ER -