Zinc Suppresses Apoptosis of U937 Cells Induced by Hydrogen Peroxide through an Increase of the Bcl-2/Bax Ratio

doi:10.1006/bbrc.1998.8621

Biochemical and Biophysical Research Communications

Volume 246, Issue 2, 19 May 1998, Pages 364-369

https://doi.org/10.1006/bbrc.1998.8621 Get rights and content

Abstract

Treatment of human premonocytic U937 cells with 500μM H₂O₂for 1h followed by 4h incubation in fresh medium to allow the cells to execute apoptotic processes caused DNA fragmentation. However, in the presence of 1mM ZnSO₄throughout the incubation, DNA ladder formation was markedly inhibited. Hydrogen peroxide treatment for 1h with or without zinc increased both Bcl-2 and Bax proteins. However, only Bax protein decreased to basal levels in the presence of zinc during the following 4h incubation, resulting in an increase of the Bcl-2/Bax ratio and prevention of apoptosis. Treatment of U937 cells with 1mM ZnSO₄alone also decreased the levels of Bax protein. Furthermore, we observed that zinc completely inhibited the activation of CPP32 by H₂O₂, while no significant changes of ICE activities occurred with either H₂O₂and/or zinc. These results indicate that the suppression of H₂O₂-induced apoptosis by zinc is mediated through an increase of the Bcl-2/Bax ratio, which occurs upstream from the activation of CPP32.

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^☆: Abbreviations used: ICE, interleukin 1β converting enzyme; PARP, poly (ADP-ribose) polymerase; HSP70, heat shock protein 70; NF-κB, nuclear factor-κB; PBS, phosphate-buffered saline; PI, propidium iodide

¹: To whom correspondence should be addressed at Department of Biochemistry, School of Medicine, University of Occupational and Environmental Health, Iseigaoka 1-1, Yahatanishi-ku, Kitakyushu 807, Japan. Fax: 81-093-692-2777. E-mail:[email protected].

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Regular ArticleZinc Suppresses Apoptosis of U937 Cells Induced by Hydrogen Peroxide through an Increase of the Bcl-2/Bax Ratio☆

Abstract

J. Biol. Chem.

Anal. Biochem.

Life Sci.

J. Biol. Chem.

J. Biol. Chem.

FEBS Lett.

Ann. Clin. Lab. Sci.

J. Pathol.

Lab. Invest.

J. Immunol.

Cell Death Differentiation.

Cell Growth Differentiation

Rad. Res.

Nucleic Acid Res.

Nature

Regular Article
Zinc Suppresses Apoptosis of U937 Cells Induced by Hydrogen Peroxide through an Increase of the Bcl-2/Bax Ratio☆