Different carbon chain length alcohols modify histone H3 acetylation via histone acetyl transferase (HAT) and also sensitize ethanol induced acetylation in rat hepatocytes

Abstract

Ethanol increases histone H3 acetylation in rat liver. However, effects of other carbon chain length alcohols, found in surrogate drinks and also used in industry, on H3 acetylation are unknown. Hence, we investigated their effect on acetylation, alone and in combination with ethanol. Primary culture of rat hepatocytes were incubated, separately, with a selected dose (40 mM) of methanol, ethanol, propanol, butanol, pentanol, hexanol or octanol for 24 hrs. Histone H3 acetylation at specific lysine residues were monitored by western blot using site specific antibodies. Ratio of acetylated lysine residues / β-actin was calculated. Increasing chain length alcohols showed a biphasic effect on H3 acetylation at lys9 but not at lys14, lys18, lys23 or lys27. Propanol showed highest increase. At 40 mM, propanol caused a 3 fold increase (in ratio), and also increased HAT activity by 4.7 fold, over control. All of these alcohols had negligible effect on histone deacetylase activity. Low concentration (2.5 mM) of propanol alone did not affect acetylation, but sensitized ethanol induced H3-lys9 acetylation. Butanol and isopentanol also sensitized ethanol response. In conclusion, different carbon chain length alcohols modulate histone H3-lys9 acetylation via altering HAT activity and some of these alcohols can also sensitize ethanol induced H3 acetylation in hepatocytes. Supported by NIH grants AA14852 and AA11962.