Increase in class 2 aldehyde dehydrogenase expression by arachidonic acid in rat hepatoma cells

Aldehyde dehydrogenase (ALDH) is a family of several isoenzymes important i n cell defence against both exogenous and endogenous aldehydes. Compared wi th normal hepatocytes, in rat hepatoma cells the following changes in the e xpression of ALDH occur: cytosolic class 3 ALDH expression appears and mito chondrial class 2 ALDH decreases. In parallel with these changes, a decreas e in the polyunsaturated fatty acid content in membrane phospholipids occur s. In the present study we demonstrated that restoring the levels of arachi donic acid in 7777 and JM2 rat hepatoma cell lines to those seen in hepatoc ytes decreases hepatoma cell growth, and increases class 2 ALDH activity. T his latter effect appears to be due to an increased gene transcription of c lass 2 ALDH. To account for this increase, we examined whether peroxisome-p roliferator-activated receptors (PPARs) or lipid peroxidation were involved . We demonstrated a stimulation of PPAR expression, which is different in t he two hepatoma cell lines: in the 7777 cell line, there was an increase in PPAR alpha expression, whereas PPAR gamma expression increased in JM2 cell s. We also found increased lipid peroxidation, but this increase became evi dent at a later stage when class 2 ALDH expression had already increased. I n conclusion, arachidonic acid added to the culture medium of hepatoma cell lines is able to partially restore the normal phenotype of class 2 ALDH, i n addition to a decrease in cell growth.