Metallothionein overexpression and resistance to toxic stress

J. H. Beattie, H. L. H. Owen, S. M. Wallace, I. -. S. Kwun, Gabrielle Margaret Hawksworth, Heather Mann Wallace

Research output: Contribution to journalArticle

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Abstract

Metallothionein (MT) protects against the harmful effects of a wide spectrum of stress factors. The most studied of these factors is cadmium, whose toxicity is reduced on sequestration by MT. However, there is poorer consensus in the literature about protection afforded by NIT against stressors other than cadmium. In this study, a CHO-K1 cell line continuously overexpressing MT (MToex) was developed in order to evaluate the relative protection afforded by MT against different toxic agents. Cadmium was used as a positive control and, as expected, the MToex cells were more than 13-fold more resistant to the effects of cadmium chloride than were wild-type (WT) cells using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay (IC50 values of 10 and 132 mu M for WT and MToex cells, respectively). In contrast, overexpression of MT afforded no protection against mercuric chloride, staurosporine and hydrogen peroxide (IC50 values of about 50, 11 and 925 mu M, respectively). Cd and Hg uptake by MToex and WT cells exposed to 1-10 mu M of metal chloride was similar and yet a significant amount of these metals was associated with the cytosol NIT fraction in the MToex cells but not in the WT cells. From this study it can be concluded that while MT overexpression protects against Cd toxicity, it has no influence on Hg, staurosporine or hydrogen peroxide toxicity and it is proposed that this reflects mechanistic differences of toxicity or depletion of labile intracellular zinc by the presence of excess binding ligand in the form of MT. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

Original languageEnglish
Pages (from-to)69-78
Number of pages9
JournalToxicology Letters
Volume157
DOIs
Publication statusPublished - 2005

Keywords

  • cadmium
  • mercury
  • staurosporine
  • hydrogen peroxide
  • zinc
  • cytotoxicity
  • HYDROPEROXIDE GLUTATHIONE-PEROXIDASE
  • NULL MICE
  • OXIDATIVE STRESS
  • TRANSGENIC MICE
  • INCREASED SENSITIVITY
  • SUPEROXIDE-DISMUTASE
  • INORGANIC MERCURY
  • GENE-EXPRESSION
  • IN-VITRO
  • CADMIUM

Cite this

Beattie, J. H., Owen, H. L. H., Wallace, S. M., Kwun, I. . S., Hawksworth, G. M., & Wallace, H. M. (2005). Metallothionein overexpression and resistance to toxic stress. Toxicology Letters, 157, 69-78. https://doi.org/10.1016/j.toxlet.2005.01.005

Metallothionein overexpression and resistance to toxic stress. / Beattie, J. H.; Owen, H. L. H.; Wallace, S. M.; Kwun, I. -. S.; Hawksworth, Gabrielle Margaret; Wallace, Heather Mann.

In: Toxicology Letters, Vol. 157, 2005, p. 69-78.

Research output: Contribution to journalArticle

Beattie, JH, Owen, HLH, Wallace, SM, Kwun, IS, Hawksworth, GM & Wallace, HM 2005, 'Metallothionein overexpression and resistance to toxic stress', Toxicology Letters, vol. 157, pp. 69-78. https://doi.org/10.1016/j.toxlet.2005.01.005
Beattie, J. H. ; Owen, H. L. H. ; Wallace, S. M. ; Kwun, I. -. S. ; Hawksworth, Gabrielle Margaret ; Wallace, Heather Mann. / Metallothionein overexpression and resistance to toxic stress. In: Toxicology Letters. 2005 ; Vol. 157. pp. 69-78.
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T1 - Metallothionein overexpression and resistance to toxic stress

AU - Beattie, J. H.

AU - Owen, H. L. H.

AU - Wallace, S. M.

AU - Kwun, I. -. S.

AU - Hawksworth, Gabrielle Margaret

AU - Wallace, Heather Mann

PY - 2005

Y1 - 2005

N2 - Metallothionein (MT) protects against the harmful effects of a wide spectrum of stress factors. The most studied of these factors is cadmium, whose toxicity is reduced on sequestration by MT. However, there is poorer consensus in the literature about protection afforded by NIT against stressors other than cadmium. In this study, a CHO-K1 cell line continuously overexpressing MT (MToex) was developed in order to evaluate the relative protection afforded by MT against different toxic agents. Cadmium was used as a positive control and, as expected, the MToex cells were more than 13-fold more resistant to the effects of cadmium chloride than were wild-type (WT) cells using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay (IC50 values of 10 and 132 mu M for WT and MToex cells, respectively). In contrast, overexpression of MT afforded no protection against mercuric chloride, staurosporine and hydrogen peroxide (IC50 values of about 50, 11 and 925 mu M, respectively). Cd and Hg uptake by MToex and WT cells exposed to 1-10 mu M of metal chloride was similar and yet a significant amount of these metals was associated with the cytosol NIT fraction in the MToex cells but not in the WT cells. From this study it can be concluded that while MT overexpression protects against Cd toxicity, it has no influence on Hg, staurosporine or hydrogen peroxide toxicity and it is proposed that this reflects mechanistic differences of toxicity or depletion of labile intracellular zinc by the presence of excess binding ligand in the form of MT. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

AB - Metallothionein (MT) protects against the harmful effects of a wide spectrum of stress factors. The most studied of these factors is cadmium, whose toxicity is reduced on sequestration by MT. However, there is poorer consensus in the literature about protection afforded by NIT against stressors other than cadmium. In this study, a CHO-K1 cell line continuously overexpressing MT (MToex) was developed in order to evaluate the relative protection afforded by MT against different toxic agents. Cadmium was used as a positive control and, as expected, the MToex cells were more than 13-fold more resistant to the effects of cadmium chloride than were wild-type (WT) cells using the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay (IC50 values of 10 and 132 mu M for WT and MToex cells, respectively). In contrast, overexpression of MT afforded no protection against mercuric chloride, staurosporine and hydrogen peroxide (IC50 values of about 50, 11 and 925 mu M, respectively). Cd and Hg uptake by MToex and WT cells exposed to 1-10 mu M of metal chloride was similar and yet a significant amount of these metals was associated with the cytosol NIT fraction in the MToex cells but not in the WT cells. From this study it can be concluded that while MT overexpression protects against Cd toxicity, it has no influence on Hg, staurosporine or hydrogen peroxide toxicity and it is proposed that this reflects mechanistic differences of toxicity or depletion of labile intracellular zinc by the presence of excess binding ligand in the form of MT. (c) 2005 Elsevier Ireland Ltd. All rights reserved.

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KW - mercury

KW - staurosporine

KW - hydrogen peroxide

KW - zinc

KW - cytotoxicity

KW - HYDROPEROXIDE GLUTATHIONE-PEROXIDASE

KW - NULL MICE

KW - OXIDATIVE STRESS

KW - TRANSGENIC MICE

KW - INCREASED SENSITIVITY

KW - SUPEROXIDE-DISMUTASE

KW - INORGANIC MERCURY

KW - GENE-EXPRESSION

KW - IN-VITRO

KW - CADMIUM

U2 - 10.1016/j.toxlet.2005.01.005

DO - 10.1016/j.toxlet.2005.01.005

M3 - Article

VL - 157

SP - 69

EP - 78

JO - Toxicology Letters

JF - Toxicology Letters

SN - 0378-4274

ER -