Enhancement of oxidative damage to cultured cells and Caenorhabditis elegans by mitochondrial electron transport inhibitors.
The mechanisms that lead to mitochondrial damage under oxidative stress conditions were examined in primary and cultured cells as well as in the nematode Caenorhabditis elegans (C. elegans) treated simultaneously with electron transport inhibitors and oxygen gas. Oxygen loading enhanced the damage of PC 12 cells by thenoyltrifluoroacetone (TTFA, a complex II inhibitor), but did not by rotenone (a complex I inhibitor), antimycin (a complex III inhibitor), and sodium azide (a complex IV inhibitor). In primary hepatocytes, the enhancement was observed with the addition of sodium azide and rotenone, but not by TTFA or antimycin. In the nematode, only rotenone and TTFA enhanced the sensitivity under hyperoxia. These results demonstrate that highly specific inhibitors of electron transport can induce oxygen hypersensitivity in cell levels such as PC 12 cells and primary hepatocytes, and animal level of C. elegans. In addition the cell damage is different dependent on cell type and organism.
Ishiguro
H
H
Department of Pediatrics, Tokai University School of Medicine, Bohseidai, Isehara, Kanagawa, Japan
Yasuda
K
K
Ishii
N
N
Ihara
K
K
Ohkubo
T
T
Hiyoshi
M
M
Ono
K
K
Senoo-Matsuda
N
N
Shinohara
O
O
Yosshii
F
F
Murakami
M
M
Hartman
P S
PS
Tsuda
M
M
D000818:Animals; D000968:Antimycin A / Q000031:analogs & derivatives* / Q000494:pharmacology; D000975:Antioxidants / Q000494:pharmacology; D017173:Caenorhabditis elegans / Q000187:drug effects* / Q000378:metabolism*; D004579:Electron Transport / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D008297:Male; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism*; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress; D016716:PC12 Cells; D051381:Rats; D017208:Rats, Wistar; D012402:Rotenone / Q000494:pharmacology; D019810:Sodium Azide / Q000494:pharmacology; D013804:Thenoyltrifluoroacetone / Q000494:pharmacology
D000975:Antioxidants; D012402:Rotenone; C032456:antimycin; D009569:Nitric Oxide; D013804:Thenoyltrifluoroacetone; D000968:Antimycin A; D019810:Sodium Azide