TY - JOUR
T1 - Mitochondrial Signal Lacking Manganese Superoxide Dismutase Failed to Prevent Cell Death by Reoxygenation Following Hypoxia in a Human Pancreatic Cancer Cell Line, KP4
AU - Hirai, Futoshi
AU - Motoori, Shigeatsu
AU - Kakinuma, Shizuko
AU - Tomita, Kazuo
AU - Indo, Hiroko P.
AU - Kato, Hirotoshi
AU - Yamaguchi, Taketo
AU - Yen, Hsiu Chuan
AU - St. Clair, Daret K.
AU - Nagano, Tetsuo
AU - Ozawa, Toshihiko
AU - Saisho, Hiromitsu
AU - Majima, Hideyuki J.
PY - 2004/6
Y1 - 2004/6
N2 - 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.
AB - 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.
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U2 - 10.1089/152308604773934288
DO - 10.1089/152308604773934288
M3 - Article
C2 - 15130279
AN - SCOPUS:2442432473
SN - 1523-0864
VL - 6
SP - 523
EP - 535
JO - Antioxidants and Redox Signaling
JF - Antioxidants and Redox Signaling
IS - 3
ER -