Oxygen-dependent-regulation of Ehrlich ascites tumor cell respiration by nitric oxide.
Effects of nitric oxide (NO) on oxygen uptake of Ehrlich ascites tumor cells (EATC) were examined in a study of the biological actions of NO on respiration and energy metabolism at the cellular level. Endogenous respiration of EATC was inhibited reversibly by NO in a dose dependent manner. Oxyhemoglobin, an NO trapping agent, restored the respiration promptly. The inhibitory action of NO also depended on oxygen-concentration, and the duration of suppression was prolonged remarkably at low oxygen tension. Similar inhibition was also observed in the presence of glucose. In this case, both lactate production and glucose consumption were promoted by NOC 18, an NO generating agent, and the activation was enhanced by lowering the oxygen-concentration. Furthermore, the membrane potential of EATC was depolarized transiently by adding NO, and the degree of depolarization was decreased in the presence of glucose. These results suggest that at physiologically low oxygen tension in ascites fluid, NO acts not only as a cytotoxic respiratory inhibitor but also as a regulatory factor in the energy metabolism of EATC.
Inai
Y
Y
Department of Cell Chemistry, Okayama University Medical School, Japan.
Takehara
Y
Y
Yabuki
M
M
Sato
E F
EF
Akiyama
J
J
Yasuda
T
T
Inoue
M
M
Horton
A A
AA
Utsumi
K
K
D000818:Animals; D002286:Carcinoma, Ehrlich Tumor / Q000473:pathology; D019069:Cell Respiration / Q000187:drug effects / Q000502:physiology; D004072:Digitonin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D006019:Glycolysis / Q000187:drug effects; D007202:Indicators and Reagents / Q000494:pharmacology; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000494:pharmacology*; D010100:Oxygen / Q000378:metabolism*; D010108:Oxyhemoglobins / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000166:cytology / Q000187:drug effects / Q000378:metabolism
D007202:Indicators and Reagents; D010108:Oxyhemoglobins; D009569:Nitric Oxide; D005947:Glucose; D004072:Digitonin; D010100:Oxygen