Metallothioneins (MTs) have a major role to play in metal metabolism, and may also protect DNA against oxidative damage. MT protein has been found localized in the nucleus during S-phase. The mRNA encoding the MT-1 isoform has a perinuclear localization, and is associated with the cytoskeleton; this targeting, due to signals within the 3′-untranslated region (3′-UTR), facilitates nuclear localization of MT-1 during S-phase [Levadoux, Mahon, Beattie, Wallace and Hesketh (1999) J. Biol. Chem. 274, 34961-34966]. Using cells transfected with MT gene constructs differing in their 3′-UTRs, the role of MT protein in the nucleus has been studied. Chinese hamster ovary cells were transfected with either the full MT gene (MTMT cells) or with the MT 5′-UTR and coding region linked to the 3′-UTR of glutathione peroxidase (MTGSH cells). Cell survival following exposure to oxidative stress and chemical agents was higher in cells expressing the native MT gene than in cells where MT localization was disrupted, or in untransfected cells. Also, MTMT cells showed less DNA damage than MTGSH cells in response to either hydrogen peroxide or mutagen. After exposure to UV light or mutagen, MTMT cells showed less apoptosis than MTGSH cells, as assessed by DNA fragmentation and flow cytometry. The data indicate that the perinuclear localization of MT mRNA is important for the function of MT in a protective role against DNA damage and apoptosis induced by external stress.
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April 2001
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Research Article|
April 06 2001
Influence of metallothionein-1 localization on its function
Marilyne LEVADOUX-MARTIN;
Marilyne LEVADOUX-MARTIN
1
*Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, U.K.
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John E. HESKETH;
John E. HESKETH
1
*Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, U.K.
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John H. BEATTIE;
John H. BEATTIE
*Rowett Research Institute, Greenburn Road, Bucksburn, Aberdeen AB21 9SB, Scotland, U.K.
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Heather M. WALLACE
Heather M. WALLACE
2
†Department of Medicine and Therapeutics and Biomedical Sciences, University of Aberdeen, Polwarth Building, Aberdeen AB25 2ZD, Scotland, U.K.
2To whom correspondence should be addressed (e-mail h.m.wallace@abdn.ac.uk).
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Publisher: Portland Press Ltd
Received:
October 26 2000
Revision Received:
December 18 2000
Accepted:
January 31 2001
Online ISSN: 1470-8728
Print ISSN: 0264-6021
The Biochemical Society, London © 2001
2001
Biochem J (2001) 355 (2): 473–479.
Article history
Received:
October 26 2000
Revision Received:
December 18 2000
Accepted:
January 31 2001
Citation
Marilyne LEVADOUX-MARTIN, John E. HESKETH, John H. BEATTIE, Heather M. WALLACE; Influence of metallothionein-1 localization on its function. Biochem J 15 April 2001; 355 (2): 473–479. doi: https://doi.org/10.1042/bj3550473
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