ACETALDEHYDE-PROTEIN ADDUCTS, BUT NOT LACTATE AND PYRUVATE, STIMULATEGENE-TRANSCRIPTION OF COLLAGEN AND FIBRONECTIN IN HEPATIC FAT-STORINGCELLS

Hepatic fibrosis is an important morphological feature of alcohol-indu ced liver injury. We previously reported that acetaldehyde, but not et hanol can stimulate type I collagen and fibronectin synthesis in cultu res of rat fat-storing cells (FSC) by increasing transcription of the specific genes. The effect of lactate and pyruvate was studied on coll agen I, III, fibronectin accumulation by cultured rat FSCs and it was investigated whether acetaldehyde could increase procollagen I and fib ronectin gene transcription through the formation of protein adducts. Lactate and pyruvate (5, 15 and 25 mmol/l) did not significantly affec t collagen I, III and fibronectin production by cultured FSCs. Pyridox al-phosphate and p-hydroxymecuribenzoate (inhibitors of acetaldehyde-p rotein adduct formation) blocked the stimulatory effect of acetaldehyd e on procollagen I and fibronectin gene transcription. These data sugg est that ethanol may act as a liver fibrogenic factor through acetalde hyde, its immediate metabolite, whereas lactate does not seem to play a role. Acetaldehyde might stimulate gene transcription of extracellul ar matrix components by liver FSCs through the formation of adducts wi th proteins.