Control of respiration by nitric oxide in Keilin-Hartree particles, mitochondria and SH-SY5Y neuroblastoma cells.
The pattern of cytochrome c oxidase inhibition by nitric oxide (NO) was investigated polarographically using Keilin-Hartree particles, mitochondria and human neuroblastoma cells. NO reacts with purified cytochrome c oxidase forming either a nitrosyl- or a nitrite-inhibited derivative, displaying distinct kinetics and light sensitivity of respiration recovery in the absence of free NO. Keilin-Hartree particles or cells, respiring either on endogenous substrates alone or in the presence of ascorbate, as well as state 3 and state 4 mitochondria respiring on glutamate and malate, displayed the rapid recovery characteristic of the nitrite derivative. All systems, when respiring in the presence of tetramethyl-p-phenylenediamine, were characterised by the slower, light-sensitive recovery typical of the nitrosyl derivative. Together the results suggest that the reaction of NO with cytochrome c oxidase in situ follows two alternative inhibition pathways, depending on the electron flux through the respiratory chain.
D000818:Animals; D002417:Cattle; D019069:Cell Respiration / Q000502:physiology*; D003576:Electron Transport Complex IV / Q000037:antagonists & inhibitors; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008930:Mitochondria, Liver / Q000378:metabolism*; D008954:Models, Biological; D009206:Myocardium / Q000378:metabolism; D009447:Neuroblastoma / Q000378:metabolism*; D009569:Nitric Oxide / Q000378:metabolism*; D011048:Polarography; D051381:Rats; D017208:Rats, Wistar; D014407:Tumor Cells, Cultured
D009569:Nitric Oxide; D003576:Electron Transport Complex IV