Human hepatic stellate cells express class I alcohol dehydrogenase and aldehyde dehydrogenase but not cytochrome P4502E1.
OBJECTIVE
Alcohol dehydrogenase, cytochrome P4502E1 (CYP2E1), and aldehyde dehydrogenase are known to play an important role in alcohol metabolism in the liver. Although the ethanol oxidation pathways are mainly localized in hepatocytes, we examine whether human hepatic stellate cells might also metabolize ethanol and acetaldehyde.


METHODS
Hepatic stellate cells were isolated from normal human livers and exposed in vitro to 50 mmol/l ethanol or 85 micromol/l acetaldehyde for different periods of time. Alcohol dehydrogenase/aldehyde dehydrogenase activity and CYP2E1 protein expression were measured in hepatic stellate cells. Moreover, alcohol dehydrogenase and aldehyde dehydrogenase mRNA expression were evaluated in hepatic stellate cells.


RESULTS
Exposure 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 increase in the alcohol dehydrogenase mRNA expression in hepatic stellate cells. Acetaldehyde significantly increased the activity of high affinity aldehyde dehydrogenase in hepatic stellate cells, whereas ethanol was devoid of any effect. Acetaldehyde also induced high affinity aldehyde 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.
Casini
A
A
Centro di Alcologia, Dip. Fisiopatologia Clinica, Università di Firenze, Italy.
Pellegrini
G
G
Ceni
E
E
Salzano
R
R
Parola
M
M
Robino
G
G
Milani
S
S
Dianzani
M U
MU
Surrenti
C
C
D000079:Acetaldehyde / Q000494:pharmacology*; D000426:Alcohol Dehydrogenase / Q000032:analysis / Q000096:biosynthesis*; D002478:Cells, Cultured; D019392:Cytochrome P-450 CYP2E1 / Q000032:analysis / Q000096:biosynthesis; D000431:Ethanol / Q000494:pharmacology*; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D006801:Humans; D008099:Liver / Q000166:cytology* / Q000201:enzymology*; D012333:RNA, Messenger / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects
D012333:RNA, Messenger; D000431:Ethanol; D000426:Alcohol Dehydrogenase; D019392:Cytochrome P-450 CYP2E1; D000079:Acetaldehyde