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

 Sun Young Park  ;  Inik Chang  ;  Myung-Shik Lee  ;  Keshav Singh  ;  Se-Ho Park  ;  Sang Won Kang  ;  Ja-Young Kim 
 JOURNAL OF BIOLOGICAL CHEMISTRY, Vol.279(9) : 7512-7520, 2004 
Journal Title
Issue Date
Animals ; Apoptosis* ; Blotting, Western ; Carcinoma, Hepatocellular ; DNA, Mitochondrial/analysis* ; DNA, Mitochondrial/physiology* ; Doxorubicin/pharmacology ; Drug Resistance ; Gene Expression ; Glutathione Peroxidase/genetics ; Hydrogen Peroxide/metabolism ; Hydrogen Peroxide/pharmacology ; Insulinoma ; Liver Neoplasms ; Mice ; Oxidative Stress ; Pancreatic Neoplasms ; Paraquat/pharmacology ; Reactive Oxygen Species/analysis ; Reactive Oxygen Species/pharmacology ; Reverse Transcriptase Polymerase Chain Reaction ; Superoxide Dismutase/genetics ; Superoxides/analysis ; Superoxides/metabolism ; Tumor Cells, Cultured ; Vitamin K 3/pharmacology
We have shown that mitochondrial DNA-depleted (rho(0)) SK-Hep1 hepatoma cells are resistant to apoptosis, contrary to previous papers reporting normal apoptotic susceptibility of rho(0) cells. We studied the changes of gene expression in SK-Hep1 rho(0) cells. DNA chip analysis showed that MnSOD expression was profoundly increased in rho(0) cells. O(2)(.) contents increased during rho(0) cell derivation but became normalized after establishment of rho(0) phenotypes, suggesting that MnSOD induction is an adaptive process to increased O(2)(.). rho(0) cells were resistant to menadione, paraquat, or doxorubicin, and O(2)(.) contents after treatment with them were lower in rho(0) cells compared with parental cells because of MnSOD overexpression. Expression levels and activity of glutathione peroxidases were also increased in rho(0) cells, rendering them resistant to exogenous H(2)O(2). rho(0) cells were resistant to p53, and intracellular ROS contents after p53 expression were lower compared with parental cells. Other types of rho(0) cells also showed increased MnSOD expression and resistance against ROS. Heme oxygenase-1 expression was increased in rho(0) cells, and a heme oxygenase-1 inhibitor decreased the induction of MnSOD in rho(0) cells and their resistance against ROS donors. These results indicate that rho(0) 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
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2. College of Dentistry (치과대학) > Dept. of Oral Biology (구강생물학교실) > 1. Journal Papers
Yonsei Authors
Chang, In Ik(장인익)
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