Augmentation of urea-synthetic capacity by inhibition of nitric oxide synthesis in butyrate-induced differentiated human hepatocytes.
We have recently developed an in vitro differentiation model of immortalized non-transformed human hepatocytes using butyrate, and observed the induction of inducible NO synthase (iNOS). In this study, we analyzed the effect of NO on the urea-synthetic capacity of these cells. The inhibition of iNOS during butyrate treatment significantly increased the urea-synthetic capacity as compared to that of butyrate treatment alone, possibly through the further induction of ornithine transcarbamylase expression. Therefore, the inhibition of NO production might be useful for obtaining more differentiated hepatocytes in the process of in vitro induction of hepatocyte-specific differentiation.
Yoon
J H
JH
Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 28 Yungun-dong Chongno-gu, 110-744, Seoul, South Korea.
Lee
H S
HS
Kim
T H
TH
Woo
G H
GH
Kim
C Y
CY
D001124:Argininosuccinate Synthase / Q000235:genetics; D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D020148:Butyric Acid / Q000494:pharmacology*; D022762:CCAAT-Enhancer-Binding Proteins; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000235:genetics; D004790:Enzyme Induction / Q000187:drug effects; D004815:Epidermal Growth Factor / Q000494:pharmacology; D019833:Genistein / Q000494:pharmacology; D051557:Hepatocyte Nuclear Factor 4; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D009569:Nitric Oxide / Q000096:biosynthesis* / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000378:metabolism / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D009573:Nitrites / Q000378:metabolism; D009687:Nuclear Proteins / Q000235:genetics; D009954:Ornithine Carbamoyltransferase / Q000235:genetics; D010750:Phosphoproteins / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics; D015533:Transcriptional Activation / Q000187:drug effects; D014508:Urea / Q000378:metabolism*
D051778:Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; D022762:CCAAT-Enhancer-Binding Proteins; D004268:DNA-Binding Proteins; D051557:Hepatocyte Nuclear Factor 4; C403128:MLX protein, human; D016328:NF-kappa B; D020030:Nitric Oxide Donors; D009573:Nitrites; D009687:Nuclear Proteins; D010750:Phosphoproteins; D012333:RNA, Messenger; D014157:Transcription Factors; D020148:Butyric Acid; D009569:Nitric Oxide; D004815:Epidermal Growth Factor; D014508:Urea; D019833:Genistein; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D009954:Ornithine Carbamoyltransferase; D001124:Argininosuccinate Synthase