Nitric oxide inhibits expression of cytochrome B in endotoxin-stimulated murine macrophages.
In LPS-mediated states of sepsis, inducible nitric oxide synthase (iNOS) expression and nitric oxide (NO) production inhibit cellular respiration and mitochondrial electron transport. NO has been demonstrated to inhibit mitochondrial respiration by nitrosylation of the iron-sulfur centers of aconitase, complex I (NADH-ubiquinone oxidoreductase), complex II (succinate-ubiquinone oxidoreductase), and complex IV (cytochrome c oxidase). However, little is known of the effect of NO on expression of critical proteins in the electron transport chain. In ANA-1 murine macrophages, LPS-mediated NO synthesis decreases Cyt b protein expression and steady-state mRNA levels. Mitochondrial run-on analysis demonstrates unaltered Cyt b mitochondrial gene transcription. In this study utilizing LPS-stimulated ANA-1 murine macrophages, we demonstrate that expression of the mitochondrial protein, Cyt b, is significantly decreased as the result of a unique and previously unknown, NO-dependent posttranscriptional regulatory mechanism. (c)2001 Elsevier Science.
Guo
H
H
Department of Surgery, Duke University Medical Center, Durham, North Carolina 27710, USA.
Wei
J
J
Kuo
P C
PC
D000818:Animals; D002460:Cell Line; D019069:Cell Respiration / Q000187:drug effects; D003573:Cytochrome b Group / Q000235:genetics* / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004579:Electron Transport / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000633:toxicity; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects
D003573:Cytochrome b Group; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D009569:Nitric Oxide