Cited by 253Mitochondrial Function and PathologyCancer and biochemical researchRedox biology and oxidative stress

A Mutation in the SDHC Gene of Complex II Increases Oxidative Stress, Resulting in Apoptosis and Tumorigenesis

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Ishii, Takamasa, Yasuda, Kayo, Akatsuka, Akira, Hino, Okio, Hartman, Philip S., Ishii, Naoaki·2005·Cancer Research

Abstract

Intracellular oxidative stress from mitochondria is thought to be important in carcinogenesis and tumorigenesis, but direct experimental proof is limited. In this study, a transgenic mouse cell line (SDHC E69) with a mutated SDHC gene (a subunit of complex II in the electron transport chain) was constructed to test this question. The SDHC E69 cells overproduced superoxide anion (O2−) from mitochondria, had elevated cytoplasmic carbonyl proteins and 8-OH-deoxyguanine in their DNA as well as significantly higher mutation frequencies than wild type. There were many apoptotic cells in this cell line, as predicted by the observed increase in caspase 3 activity, decrease in mitochondrial membrane potential, and structural changes in their mitochondria. In addition, some cells that escaped from apoptosis underwent transformation, as evidenced by the fact that SDHC E69 cells caused benign tumors when injected under the epithelium of nude mice. These results underscore the notion that mitochondrially generated oxidative stress can contribute to nuclear DNA damage, mutagenesis, and ultimately, tumorigenesis.

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Research works printed but not linked: 2

  1. Simonian NA, Coyle JT. Oxidative stress in neurode- generative diseases. Annu Rev Pharmacol Toxicol 1996; 36:83-106.
  2. Mattson MP. Apoptosis in neurodegenerative disor- ders. Nat Rev Mol Cell Biol 2000;1:120-9.

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Authors
Ishii, T., Yasuda, K., Akatsuka, A., Hino, O., Hartman, P. S., & Ishii, N.
Affiliations
  • 1Department of Molecular Life Science and
  • Tokai University (JP)
  • Japanese Foundation For Cancer Research (JP)
  • Texas Christian University (US)
Venue
Cancer Research
Published
2005-01-01
Volume
65
Issue
1
Pages
203-209
ISSN
  • 0008-5472 (ISSN-L)
  • 1538-7445
OpenAlex
W2116622745
Cited by
253
References
55
Citations by year
2026: 5 · 2025: 8 · 2024: 8 · 2023: 7 · 2022: 7 · 2021: 15 · 2020: 9 · 2019: 7 · 2018: 11 · 2017: 11 · 2016: 13 · 2015: 9 · 2014: 21 · 2013: 12 · 2012: 19
FWCI
6.65
Type
journal article
Language
en
Open access
Locations
  • Cancer Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • Boehringer Ingelheim Japan
  • Ministry of Education, Culture, Sports, Science and Technology
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cancer and biochemical research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
Keywords
succinate dehydrogenase, oxidative stress, apoptosis, carcinogenesis, superoxide, mitochondrial DNA damage, protein carbonylation, caspase-3, mitochondrial membrane potential
MeSH terms
8-Hydroxy-2'-Deoxyguanosine, Amino Acid Sequence, Animals, Bacterial Proteins, Base Sequence, Cloning, Molecular, Deoxyguanosine, Gene Frequency, Humans, Membrane Proteins, Mice, Transgenic, Molecular Sequence Data, Neoplasms, Succinate Dehydrogenase, Superoxides, Polymerase Chain Reaction, Sequence Alignment, Apoptosis, Sequence Homology, Amino Acid, DNA Primers, Oxidative Stress, Caspases, Mice, Caspase 3

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