Rapid induction of NF-kappaB binding during liver cell isolation and culture: inhibition by L-NAME indicates a role for nitric oxide synthase.
This study is the first to demonstrate activation of NF-kappaB binding just 10 minutes into the commonly employed hepatocyte isolation procedure. It is further reported that the anti-oxidant Trolox can prevent the induction of NF-kappaB during the well established hepatocyte isolation procedure but not during their subsequent culture. However both phases of NF-kappaB activation are inhibited by L-NAME intimating a role for NO production, via nitric oxide synthase. These findings demonstrate that at least 2 different signal transduction pathways are operative during hepatocyte isolation and culture. Thus further studies employing Trolox and L-NAME will help delineate how each pathway contributes to the generalised loss of liver function commonly observed in vitro.
Rodriguez-Ariza
A
A
Division of Pharmacology, School of Medicine and Dentistry, Queen Mary & Westfield College, Charterhouse Square, London, EC1M 6BQ, United Kingdom.
Paine
A J
AJ
D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D001667:Binding, Competitive; D018929:Cell Culture Techniques; D002469:Cell Separation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002839:Chromans / Q000494:pharmacology; D004229:Dithiothreitol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008099:Liver / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D008297:Male; D016328:NF-kappa B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D019331:NG-Nitroarginine Methyl Ester / Q000031:analogs & derivatives / Q000494:pharmacology*; D009566:Nitrates / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009841:Oligonucleotides / Q000235:genetics / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D020218:Response Elements / Q000235:genetics; D013997:Time Factors
D000975:Antioxidants; D002839:Chromans; D004791:Enzyme Inhibitors; D016328:NF-kappa B; D009566:Nitrates; D009841:Oligonucleotides; C039642:peroxynitric acid; D019001:Nitric Oxide Synthase; C010643:6-hydroxy-2,5,7,8-tetramethylchroman-2-carboxylic acid; D004229:Dithiothreitol; D019331:NG-Nitroarginine Methyl Ester; D000111:Acetylcysteine