Top

Research Article

Split Viewer

Mol. Cells 2004; 18(2): 220-229

Published online January 1, 1970

© The Korean Society for Molecular and Cellular Biology

Deregulation of Catalase, Not MnSOD, Is Associated with Necrotic Death of p53-defective DF-1 Cells under Antimycin A-induced Oxidative Stress

Seungkwon You, Byung-Whi Kong, Sun-Young Jeon, Douglas N. Foster, Hyunggee Kim

Abstract

One of distinct genetic alterations in spontaneously immortalized DF-1 cells was found to be dysfunction of p53 and E2F-1 as well as altered antioxidant gene expression (upregulation of MnSOD and downregulation of catalase). We have characterized the cellular responses of primary and immortal DF-1 cells to oxidative stress and found that DF-1 cells were more sensitive to oxidative stress than their primary counterparts when treated with antimycin A. The increased DF-1 cell death by oxidative stress was accompanied by an increase in the levels of intracellular superoxide anions and hydrogen peroxide. The cell death in DF-1 cells by antimycin A showed none of the hallmarks of apoptosis, but displayed a significantly increased necrotic cell population. Anti-apoptotic Bcl-2 failed to inhibit oxidative-induced necrotic cell death in the DF-1 cells. However, this necrotic cell death was significantly decreased by treatment with hydrogen peroxide scavengers such as sodium pyruvate and N-acetyl-cysteine. Interestingly, overexpression of human catalase in DF-1 cells endowed cells resistant to the oxidative stress by antimycin A treatment, although the downregulation of MnSOD by an antisense strategy showed no evident change in the cytotoxic effect caused by antimycin A. Taken together, the present study might provide new therapeutic approach for tumor cells having the loss of p53 function and the altered antioxidant functions.

Keywords Antimycin A; Bcl-2; Catalase; DF-1 Cells; Hydrogen Peroxide; Mitochondria; MnSOD; p53; Superoxide Anion

Article

Research Article

Mol. Cells 2004; 18(2): 220-229

Published online October 31, 2004

Copyright © The Korean Society for Molecular and Cellular Biology.

Deregulation of Catalase, Not MnSOD, Is Associated with Necrotic Death of p53-defective DF-1 Cells under Antimycin A-induced Oxidative Stress

Seungkwon You, Byung-Whi Kong, Sun-Young Jeon, Douglas N. Foster, Hyunggee Kim

Abstract

One of distinct genetic alterations in spontaneously immortalized DF-1 cells was found to be dysfunction of p53 and E2F-1 as well as altered antioxidant gene expression (upregulation of MnSOD and downregulation of catalase). We have characterized the cellular responses of primary and immortal DF-1 cells to oxidative stress and found that DF-1 cells were more sensitive to oxidative stress than their primary counterparts when treated with antimycin A. The increased DF-1 cell death by oxidative stress was accompanied by an increase in the levels of intracellular superoxide anions and hydrogen peroxide. The cell death in DF-1 cells by antimycin A showed none of the hallmarks of apoptosis, but displayed a significantly increased necrotic cell population. Anti-apoptotic Bcl-2 failed to inhibit oxidative-induced necrotic cell death in the DF-1 cells. However, this necrotic cell death was significantly decreased by treatment with hydrogen peroxide scavengers such as sodium pyruvate and N-acetyl-cysteine. Interestingly, overexpression of human catalase in DF-1 cells endowed cells resistant to the oxidative stress by antimycin A treatment, although the downregulation of MnSOD by an antisense strategy showed no evident change in the cytotoxic effect caused by antimycin A. Taken together, the present study might provide new therapeutic approach for tumor cells having the loss of p53 function and the altered antioxidant functions.

Keywords: Antimycin A, Bcl-2, Catalase, DF-1 Cells, Hydrogen Peroxide, Mitochondria, MnSOD, p53, Superoxide Anion

Mol. Cells
Jan 31, 2023 Vol.46 No.1, pp. 1~67
COVER PICTURE
RNAs form diverse shapes and play multiple functions as central molecules of gene expression. In this special issue on RNA, seven minireviews illustrate how basic concepts and recent RNA biology findings are transformed into new and exciting RNA therapeutics.

Share this article on

  • line
  • mail

Molecules and Cells

eISSN 0219-1032
qr-code Download