Effects of acute doxorubicin treatment on hepatic proteome lysine acetylation status and the apoptotic environment

Core Tip

Core tip: Doxorubicin (Dox) is an effective chemotherapeutic agent, but known to cause cardiotoxicity and hepatotoxicity. Cellular stress can alter proteome acetylation status in various experimental models, which has been associated with a proapoptotic environment. The effects of Dox on hepatic lysine acetylation status has not been studied. The study revealed five interesting findings that open the door for new areas of investigation: (1) Dox induces proteome lysine deacetylation; (2) lysine deacetylation is, at least in part, due to a decrease in histone acetyltransferase activity; (3) lysine deacetylation is likely not associated with an apoptotic environment; (4) Dox-induced hepatic injury is associated with caspase-12 activation; and (5) caspase-12 activation is not involved in apoptosis induction. These results may in the future translate to lysine acetylation homeostasis and/or caspase-12 as therapeutic targets.