Characterization of oxygen-resistant Chinese hamster ovary cells. III. Relative resistance of succinate and alpha-ketoglutarate dehydrogenases to hyperoxic inactivation.
We have recently shown that exposure of Chinese hamster ovary (CHO) cells to a toxic dose of normobaric hyperoxia (98% O2 for 3 days) caused a disturbance of cellular energy metabolism, that is, respiratory failure followed by stimulation of glycolytic activity and a net depletion of ATP. Respiratory failure was correlated with a selective inactivation of three mitochondrial enzymes, that is, partial inactivation of NADH dehydrogenase and virtually complete inactivation of succinate and alpha-ketoglutarate dehydrogenase activities (Schoonen et al., 1990). To elucidate the biochemical basis of resistance to hyperoxia in a previously described oxygen-resistant substrain of Chinese hamster ovary (CHO) cells, we compared the resistant cells with wildtype CHO cells with respect to several key parameters of oxidative and glycolytic energy metabolism. The two cell types were critically different in that the succinate and alpha-ketoglutarate dehydrogenases of the oxygen-resistant cells were relatively resistant to inactivation by hyperoxia, which may at least partly explain their enhanced capacity to respire and survive under hyperoxic conditions. Although the biochemical basis for the observed enzyme resistance to hyperoxic inactivation remains to be elucidated, the present data underscore the importance of succinate and alpha-ketoglutarate dehydrogenases as critical targets in hyperoxic killing of wildtype CHO cells.
Schoonen
W G
WG
Institute of Human Genetics, Free University, Amsterdam, The Netherlands.
Wanamarta
A H
AH
van der Klei-van Moorsel
J M
JM
Jakobs
C
C
Joenje
H
H
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D002463:Cell Membrane Permeability / Q000187:drug effects; D006224:Cricetinae; D004072:Digitonin / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005260:Female; D005947:Glucose / Q000378:metabolism; D006019:Glycolysis / Q000187:drug effects; D007655:Ketoglutarate Dehydrogenase Complex / Q000037:antagonists & inhibitors*; D009245:NADH Dehydrogenase / Q000037:antagonists & inhibitors; D010053:Ovary; D010100:Oxygen / Q000494:pharmacology*; D010101:Oxygen Consumption / Q000187:drug effects; D013053:Spectrophotometry; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors*
D000255:Adenosine Triphosphate; D007655:Ketoglutarate Dehydrogenase Complex; D013385:Succinate Dehydrogenase; D009245:NADH Dehydrogenase; D005947:Glucose; D004072:Digitonin; D010100:Oxygen