Hepatocellular Na+/H+ exchange is activated at transcriptional and posttranscriptional levels in rat biliary cirrhosis.
OBJECTIVE
Rat hepatocyte Na+/H+ exchange is activated in vitro by growth factors and in vivo following partial hepatectomy. This study explored by which mechanism(s) it is activated in a cirrhosis model characterized by chronic stimulation of hepatocyte proliferation.


METHODS
Rat hepatocytes were isolated 4 weeks after bile duct ligation or sham operation. Intracellular pH (pHi) was fluorimetrically determined, and plasma membranes and messenger RNA (mRNA) were prepared from isolated hepatocytes by standard methods.


RESULTS
Resting pHi was higher in bile duct-ligated than in control rats (7.42 +/- 0.03 vs. 7.06 +/- 0.04; P < 0.001). Although plasma membrane lipid composition and intracellular buffering capacity were similar, initial Na+/H+ exchange-mediated rates of pHi recovery following acid loading were higher in bile duct-ligated than in control rats (0.098 +/- 0.011 vs. 0.055 +/- 0.005 pH units/min; P < 0.05). The antiporter's set point was shifted approximately 0.3 pH units towards more alkaline values and its steady-state mRNA levels were doubled after bile duct ligation.


CONCLUSIONS
Hepatocellular Na+/H+ exchange is transcriptionally and posttranscriptionally activated in rat biliary cirrhosis further supporting a relationship between hepatocyte proliferation and Na+/H+ exchange activation.
Department of Clinical Pharmacology, University of Berne, Switzerland.
C
C
Elsing
J
J
Reichen
U
U
Marti
E L
EL
Renner
D000818:Animals; D001693:Biological Transport, Active; D015152:Blotting, Northern; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D006859:Hydrogen / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D017136:Ion Transport; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D008105:Liver Cirrhosis, Biliary / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D012964:Sodium / Q000378:metabolism*; D014158:Transcription, Genetic; D015533:Transcriptional Activation
D012333:RNA, Messenger; D006859:Hydrogen; D012964:Sodium