Mitochondrial Signal Lacking Manganese Superoxide Dismutase Failed to Prevent Cell Death by Reoxygenation Following Hypoxia in a Human Pancreatic Cancer Cell Line, KP4

Futoshi Hirai, Shigeatsu Motoori, Shizuko Kakinuma, Kazuo Tomita, Hiroko P. Indo, Hirotoshi Kato, Taketo Yamaguchi, Hsiu Chuan Yen, Daret K. St. Clair, Tetsuo Nagano, Toshihiko Ozawa, Hiromitsu Saisho, Hideyuki J. Majima

Research output: Contribution to journalArticlepeer-review

24 Citations (SciVal)

Abstract

One of the major characteristics of tumor is the presence of a hypoxic cell population, which is caused by abnormal distribution of blood vessels. Manganese superoxide dismutase (MnSOD) is a nuclear-encoded mitochondrial enzyme, which scavenges superoxide generated from the electron-transport chain in mitochondria. We examined whether MnSOD protects against hypoxia/reoxygenation (H/R)-induced oxidative stress using a human pancreas carcinoma-originated cell line, KP4. We also examined whether MnSOD is necessarily present in mitochondria to have a function. Normal human MnSOD and MnSOD without a mitochondrial targeting signal were transfected to KP4 cells, and reactive oxygen species, nitric oxide, lipid peroxidation, and apoptosis were examined as a function of time in air following 1 day of hypoxia as a H/R model. Our results showed H/R caused no increase in nitric oxide, but resulted in increases in reactive oxygen species, 4-hydroxy-2-nonenal protein adducts, and apoptosis. Authentic MnSOD protected against these processes and cell death, but MnSOD lacking a mitochondrial targeting signal could not. These results suggest that only when MnSOD is located in mitochondria is it efficient in protecting against cellular injuries by H/R, and they also indicate that mitochondria are primary sites of H/R-induced cellular oxidative injuries.

Original languageEnglish
Pages (from-to)523-535
Number of pages13
JournalAntioxidants and Redox Signaling
Volume6
Issue number3
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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