Bumetanide-sensitive cell swelling mediates the inhibitory effect of ethanol on proteolysis in rat liver

Gastroenterology
Stephan vom Dahl, D Häussinger

Abstract

Ethanol is known to inhibit proteolysis and to cause intracellular protein accumulation in the liver. The aim of this study was to investigate the mechanism underlying the antiproteolytic effect of ethanol. The effects of ethanol on proteolysis and cell volume were assessed in the isolated perfused rat liver by established tracer techniques. Infusion of ethanol (20 mmol/L) led to an increase of the intracellular water space by 9.3% +/- 0.4% (n = 3), which was abolished by methylpyrazole and mimicked by acetaldehyde (5 mmol/L). Ethanol-induced cell swelling was completely abolished by bumetanide (5 micromol/L), an inhibitor of Na-K-2Cl cotransport. Ethanol (20 mmol/L) inhibited proteolysis by 18.6% +/- 2.0% (n = 4) in a colchicine-sensitive way. This antiproteolytic effect was quantitatively mimicked by equipotent hyposmotic hepatocyte swelling and by acetaldehyde. Ethanol-induced inhibition of proteolysis was abolished in the presence of methylpyrazole (100 micromol/L), bumetanide (5 micromol/L), furosemide (100 micromol/L), and insulin (35 nmol/L), i.e., conditions that also prevented ethanol-induced cell swelling. Ethanol causes, via acetaldehyde, bumetanide-sensitive cell swelling, which in turn mediates the antiproteolytic ...Continue Reading

Citations

Aug 14, 2001·Journal of Cellular Biochemistry·R D KimR S Chari
Jul 1, 2011·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Hironobu Morita, Chikara Abe
Sep 4, 2001·Biological Chemistry·F SchliessD Häussinger
May 18, 2005·Alcoholism, Clinical and Experimental Research·Leimin SunNils Homann
Jun 11, 2002·Archives of Biochemistry and Biophysics·Freimut SchliessDieter Häussinger
Mar 26, 1999·Gastroenterology·D HäussingerS Vom Dahl
Sep 19, 2007·Methods in Enzymology·Freimut Schliess, Dieter Häussinger
Feb 1, 2007·The Journal of Biological Chemistry·Elisabeth T BarfodSteven D Lidofsky
May 9, 2000·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·H MoritaK Tanaka
Mar 2, 1999·Biochemical and Biophysical Research Communications·D Häussinger, F Schliess

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