DOI: 10.1073/pnas.95.6.2956. Bcl-2 expression causes redistribution of glutathione to the nucleus

Bcl-2 expression causes redistribution of glutathione to the nucleus

10.1073/pnas.95.6.2956

Crossref journal-article

Proceedings of the National Academy of Sciences

Proceedings of the National Academy of Sciences (341)

Abstract

In this study we used HeLa cells transfected with a conditional Bcl-2 expression construct to study the effects of Bcl-2 on reduced glutathione (GSH) metabolism. Our previous work demonstrated that depletion of GSH by culturing cells in tissue culture medium lacking the amino acids cysteine and methionine, essential for GSH biosynthesis, caused cells overexpressing Bcl-2 to become sensitized to apoptotic induction. Here we report that Bcl-2 also dramatically alters GSH compartmentalization. Cellular distribution of GSH, assayed by confocal microscopy, revealed that when Bcl-2 expression was suppressed GSH was uniformly distributed primarily in the cytosol, whereas overexpression of Bcl-2 led to a relocalization of GSH into the nucleus. Isolated nuclei readily accumulated radiolabeled GSH and maintained higher nuclear GSH concentration in direct relation to Bcl-2 nuclear protein levels. Moreover, exogenous GSH blocked apoptotic changes and caspase activity in isolated nuclei exposed to the pro-apoptotic protease granzyme B. Our results indicate that one of the functions of Bcl-2 is to promote sequestration of GSH into the nucleus, thereby altering nuclear redox and blocking caspase activity as well as other nuclear alterations characteristic of apoptosis. We speculate that this mechanism contributes to the suppression of apoptosis in cells with elevated Bcl-2 levels.

Bibliography

Voehringer, D. W., McConkey, D. J., McDonnell, T. J., Brisbay, S., & Meyn, R. E. (1998). Bcl-2 expression causes redistribution of glutathione to theânucleus. Proceedings of the National Academy of Sciences, 95(6), 2956â2960.

Authors 5

D. W. Voehringer (first)
D. J. McConkey (additional)
T. J. McDonnell (additional)
S. Brisbay (additional)
R. E. Meyn (additional)

References 31 Referenced 239

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M D Story, D W Voehringer, C G Malone, M L Hobbs, R E Meyn Int J Radiat Biol 66, 659–668 (1994). / Int J Radiat Biol by Story M D (1994)
D X Yin, R T Schimke Cancer Res 55, 4922–4928 (1995). / Cancer Res by Yin D X (1995)
M C Marin, A Fernandez, R J Bick, S Brisbay, L M Buja, M Snuggs, D J McConkey, A C von Eschenbach, M J Keating, T J McDonnell Oncogene 12, 2259–2266 (1996). / Oncogene by Marin M C (1996)
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M Krajewska, H G Wang, S Krajewski, J M Zapata, A Shabaik, R Gascoyne, J C Reed Cancer Res 57, 1605–1613 (1997). / Cancer Res by Krajewska M (1997)
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D deJong, F A Prins, D Y Mason, J C Reed, G B van Ommen, P M Kluin Cancer Res 54, 256–260 (1994). / Cancer Res by deJong D (1994)
A Fernandez, L J Fosdick, M C Marin, C Diaz, T J McDonnell, H N Ananthaswamy, D J McConkey Oncogene 10, 769–774 (1995). / Oncogene by Fernandez A (1995)
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10.1038/376037a0

Dates

Type	When
Created	23 years, 1 month ago (July 26, 2002, 10:40 a.m.)
Deposited	3 years, 4 months ago (April 13, 2022, 4:19 p.m.)
Indexed	2 months, 3 weeks ago (June 9, 2025, 4:05 a.m.)
Issued	27 years, 5 months ago (March 17, 1998)
Published	27 years, 5 months ago (March 17, 1998)
Published Online	27 years, 5 months ago (March 17, 1998)
Published Print	27 years, 5 months ago (March 17, 1998)

Funders 0

None

BibTeX

@article{Voehringer_1998, title={Bcl-2 expression causes redistribution of glutathione to the nucleus}, volume={95}, ISSN={1091-6490}, url={http://dx.doi.org/10.1073/pnas.95.6.2956}, DOI={10.1073/pnas.95.6.2956}, number={6}, journal={Proceedings of the National Academy of Sciences}, publisher={Proceedings of the National Academy of Sciences}, author={Voehringer, D. W. and McConkey, D. J. and McDonnell, T. J. and Brisbay, S. and Meyn, R. E.}, year={1998}, month=mar, pages={2956–2960} }

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