HUMAN HEPATIC STELLATE CELLS EXPRESS CLASS-I ALCOHOL-DEHYDROGENASE AND ALDEHYDE DEHYDROGENASE BUT NOT CYTOCHROME P4502E1

Background/Aims: Alcohol dehydrogenase, cytochrome P4502E1 (CYP2E1), a nd aldehyde dehydrogenase are known to play an important role in alcoh ol metabolism in the liver, Although the ethanol oxidation pathways ar e mainly localized in hepatocytes, we examine whether human hepatic st ellate cells might also metabolize ethanol and acetaldehyde. Methods: Hepatic stellate cells were isolated from normal human livers and expo sed in vitro to 50 mmol/l ethanol or 85 mu mol/l acetaldehyde for diff erent periods of time, Alcohol dehydrogenase/aldehyde dehydrogenase ac tivity and CYP2E1 protein expression were measured in hepatic stellate cells, Moreover, alcohol dehydrogenase and aldehyde dehydrogenase mRN A expression were evaluated in hepatic stellate cells, Results: Exposu re of hepatic stellate cells to ethanol for 24 h resulted in a 5-fold increase in cell alcohol dehydrogenase activity, The effect of ethanol on alcohol dehydrogenase activity was paralleled by a significant inc rease in the alcohol dehydrogenase mRNA expression in hepatic stellate cells, Acetaldehyde significantly increased the activity of high affi nity aldehyde dehydrogenase in hepatic stellate cells, whereas ethanol was devoid of any effect, Acetaldehyde also induced high affinity ald ehyde dehydrogenase mRNA expression in hepatic stellate cells, CYP2E1 was not expressed in hepatic stellate cells either in basal condition or after ethanol/acetaldehyde exposure. Conclusions: This study shows that human hepatic stellate cells have the capacity to metabolize both ethanol and acetaldehyde through a class I alcohol dehydrogenase-and an aldehyde dehydrogenase-oxidizing pathway, Conversely, no detectable levels of CYP2E1-associated proteins are expressed in these cells.