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Traces of copper ions deplete glutathione in human hepatoma cell cultures with low cysteine content

Hultberg, Malin LU ; Isaksson, Anders LU ; Andersson, Anders S LU and Hultberg, Björn LU (2007) In Chemico-Biological Interactions 167(1). p.56-62
Abstract
Background: Cell death induced by intracellutar glutathione depletion has been reported to be dependent on the presence of trace amounts of extracellular copper ions. Since little is known about the relationship between glutathione depletion and copper homeostasis, we have in the present study further investigated the role of low amounts of copper ions in glutathione depletion. Methods: Glutathione turnover was investigated in HeLa and hepatoma cell cultures with normal and low cysteine content in the presence of copper ions (1 and 10 mu mol/L) and two other glutathione-stimulating agents (lipoic acid and mercury ions). Results: Copper ions (10 mu mol/L) caused relatively small increases in total amount of glutathione (the sum of the... (More)
Background: Cell death induced by intracellutar glutathione depletion has been reported to be dependent on the presence of trace amounts of extracellular copper ions. Since little is known about the relationship between glutathione depletion and copper homeostasis, we have in the present study further investigated the role of low amounts of copper ions in glutathione depletion. Methods: Glutathione turnover was investigated in HeLa and hepatoma cell cultures with normal and low cysteine content in the presence of copper ions (1 and 10 mu mol/L) and two other glutathione-stimulating agents (lipoic acid and mercury ions). Results: Copper ions (10 mu mol/L) caused relatively small increases in total amount of glutathione (the sum of the intracellular and the extracellular amount of glutathione) in HeLa and hepatoma cell cultures with normal cysteine levels (420 nmol/mL) compared to control cell cultures, whereas lipoic acid and mercury ions strongly increased total glutathione in both types of cell cultures. Lower amount of total glutathione was observed in cell cultures with a lower cysteine levels (84 nmol/mL), which is similar to that in human plasma. A strongly decreased total amount of glutathione in the presence of copper ions was observed in hepatoma cell cultures with lower cysteine levels, whereas the other agents showed effects similar to those described for cell cultures with normal cysteine levels. Conclusion: Glutathione synthesis in hepatoma cell cultures is probably more sensitive to a low cysteine level than HeLa cell cultures, and the presence of copper ions further decreases the availability of cysteine probably by increasing the disultide binding to cysteine residues in extracellular proteins, which causes a further decrease of total glutathione. (c) 2007 Elsevier Ireland Ltd. All rights reserved. (Less)
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author
organization
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Contribution to journal
publication status
published
subject
keywords
hepatoma cell lines, HeLa cell lines, copper ions, glutathione
in
Chemico-Biological Interactions
volume
167
issue
1
pages
56 - 62
publisher
Elsevier
external identifiers
  • wos:000245882300006
  • scopus:33947120585
ISSN
1872-7786
DOI
10.1016/j.cbi.2007.01.005
language
English
LU publication?
yes
id
b910a9a4-ad72-4ad6-b71c-10de419bb177 (old id 663662)
date added to LUP
2007-12-13 08:45:12
date last changed
2017-01-01 06:53:29
@article{b910a9a4-ad72-4ad6-b71c-10de419bb177,
  abstract     = {Background: Cell death induced by intracellutar glutathione depletion has been reported to be dependent on the presence of trace amounts of extracellular copper ions. Since little is known about the relationship between glutathione depletion and copper homeostasis, we have in the present study further investigated the role of low amounts of copper ions in glutathione depletion. Methods: Glutathione turnover was investigated in HeLa and hepatoma cell cultures with normal and low cysteine content in the presence of copper ions (1 and 10 mu mol/L) and two other glutathione-stimulating agents (lipoic acid and mercury ions). Results: Copper ions (10 mu mol/L) caused relatively small increases in total amount of glutathione (the sum of the intracellular and the extracellular amount of glutathione) in HeLa and hepatoma cell cultures with normal cysteine levels (420 nmol/mL) compared to control cell cultures, whereas lipoic acid and mercury ions strongly increased total glutathione in both types of cell cultures. Lower amount of total glutathione was observed in cell cultures with a lower cysteine levels (84 nmol/mL), which is similar to that in human plasma. A strongly decreased total amount of glutathione in the presence of copper ions was observed in hepatoma cell cultures with lower cysteine levels, whereas the other agents showed effects similar to those described for cell cultures with normal cysteine levels. Conclusion: Glutathione synthesis in hepatoma cell cultures is probably more sensitive to a low cysteine level than HeLa cell cultures, and the presence of copper ions further decreases the availability of cysteine probably by increasing the disultide binding to cysteine residues in extracellular proteins, which causes a further decrease of total glutathione. (c) 2007 Elsevier Ireland Ltd. All rights reserved.},
  author       = {Hultberg, Malin and Isaksson, Anders and Andersson, Anders S and Hultberg, Björn},
  issn         = {1872-7786},
  keyword      = {hepatoma cell lines,HeLa cell lines,copper ions,glutathione},
  language     = {eng},
  number       = {1},
  pages        = {56--62},
  publisher    = {Elsevier},
  series       = {Chemico-Biological Interactions},
  title        = {Traces of copper ions deplete glutathione in human hepatoma cell cultures with low cysteine content},
  url          = {http://dx.doi.org/10.1016/j.cbi.2007.01.005},
  volume       = {167},
  year         = {2007},
}