Resistance of mitochondrial DNA-depleted cells against cell death: Role of mitochondrial superoxide dismutase

Sun Young Park, Inik Chang, Ja Young Kim, Sang Won Kang, Se-Ho Park, Keshav Singh, Myung Shik Lee

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Abstract

We have shown that mitochondrial DNA-depleted (ρ0) SK-Hep1 hepatoma cells are resistant to apoptosis, contrary to previous papers reporting normal apoptotic susceptibility of ρ0 cells. We studied the changes of gene expression in SK-Hep1 ρ0 cells. DNA chip analysis showed that MnSOD expression was profoundly increased in ρ0 cells. O2 .- contents increased during ρ0 cell derivation but became normalized after establishment of ρ0 phenotypes, suggesting that MnSOD induction is an adaptive process to increased 02 .-. ρ0 cells were resistant to menadione, paraquat, or doxorubicin, and O2 .- contents after treatment with them were lower in ρ 0 cells compared with parental cells because of MnSOD overexpression. Expression levels and activity of glutathione peroxidases were also increased in ρ0 cells, rendering them resistant to exogenous H 2O2. ρ0 cells were resistant to p53, and intracellular ROS contents after p53 expression were lower compared with parental cells. Other types of ρ0 cells also showed increased A1n801) expression and resistance against ROS. Heme oxygenase-1 expression was increased in ρ0 cells, and a heme oxygenase-1 inhibitor decreased the induction of MnSOD in ρ0 cells and their resistance against ROS donors. These results indicate that ρ0 cells are resistant to cell death contrary to previous reports and suggest that an adaptive increase in the expression of antioxidant enzymes renders cancer cells or aged cells with frequent mitochondrial DNA mutations to resist against oxidative stress, host anti-cancer surveillance, or chemotherapeutic agents, conferring survival advantage on them.

Original languageEnglish
Pages (from-to)7512-7520
Number of pages9
JournalJournal of Biological Chemistry
Volume279
Issue number9
DOIs
Publication statusPublished - 2004 Feb 27

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Heme Oxygenase-1
Cell death
Mitochondrial DNA
Superoxide Dismutase
Cell Death
Vitamin K 3
Paraquat
Oxidative stress
Glutathione Peroxidase
Gene expression
Doxorubicin
Antioxidants
Cells
Apoptosis
DNA
Enzymes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Resistance of mitochondrial DNA-depleted cells against cell death : Role of mitochondrial superoxide dismutase. / Park, Sun Young; Chang, Inik; Kim, Ja Young; Kang, Sang Won; Park, Se-Ho; Singh, Keshav; Lee, Myung Shik.

In: Journal of Biological Chemistry, Vol. 279, No. 9, 27.02.2004, p. 7512-7520.

Research output: Contribution to journalArticle

Park, Sun Young ; Chang, Inik ; Kim, Ja Young ; Kang, Sang Won ; Park, Se-Ho ; Singh, Keshav ; Lee, Myung Shik. / Resistance of mitochondrial DNA-depleted cells against cell death : Role of mitochondrial superoxide dismutase. In: Journal of Biological Chemistry. 2004 ; Vol. 279, No. 9. pp. 7512-7520.
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