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 con ditions were examined in primary and cultured cells as well as in the nemat ode 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 inhi bitor), 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 enh anced the sensitivity under hyperoxia. These results demonstrate that highl y specific inhibitors of electron transport can induce oxygen hypersensitiv ity 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.