| RRC ID |
42155
|
| Author |
Hirai F, Motoori S, Kakinuma S, Tomita K, Indo HP, Kato H, Yamaguchi T, Yen HC, St Clair DK, Nagano T, Ozawa T, Saisho H, Majima HJ.
|
| Title |
Mitochondrial signal lacking manganese superoxide dismutase failed to prevent cell death by reoxygenation following hypoxia in a human pancreatic cancer cell line, KP4.
|
| Journal |
Antioxid Redox Signal
|
| 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.
|
| Volume |
6(3)
|
| Pages |
523-35
|
| Published |
2004-6-1
|
| DOI |
10.1089/152308604773934288
|
| PMID |
15130279
|
| MeSH |
Aldehydes / chemistry
Apoptosis
Cell Death
Cell Line, Tumor
DNA Adducts
DNA Primers / chemistry
DNA, Complementary / metabolism
Humans
Hypoxia
Lipid Peroxidation
Microscopy, Fluorescence
Mitochondria / metabolism
Mitochondria / pathology*
Nitric Oxide / metabolism
Oxidative Stress
Oxygen / metabolism
RNA, Messenger / metabolism
Reactive Oxygen Species / metabolism
Reverse Transcriptase Polymerase Chain Reaction
Signal Transduction*
Superoxide Dismutase / metabolism
Superoxide Dismutase / physiology*
Time Factors
Transfection
|
| IF |
7.04
|
| Times Cited |
21
|
|
WOS Category
|
ENDOCRINOLOGY & METABOLISM
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| Resource |
| Human and Animal Cells |
|
