Induction of heme oxygenase-1 by acrolein mediates a cytoprotective effect in HepG2 cells

Abstract

Acrolein is an alpha, beta-unsaturated aldehyde present in cigarette smoke, and is also a product of lipid peroxidation. Heme oxygenase-1 (HO-1) plays critical roles in preventing oxidative stress and other cellular functions, and induces viability and proliferation of tumor cells. Acrolein is well-known to induce HO-1, although the signal pathway has not been fully elucidated. This study elucidated the involved signaling and acrolein’s cytoprotective effects in human hepatocellular carcinoma (HepG2) cells. Cells were treated with acrolein to induce HO-1, whose expression was measured by Western blot, RT-PCR and immunofluorescence staining analyses. Low concentrations of acrolein remarkably increased HO-1 mRNA and protein levels. Acrolein-mediated HO-1 induction was notably decreased by rottlerin and SB203580, selective inhibitors of PKC-δ and p38 MAPK, respectively. Furthermore, the cells displayed an increased arrest at the G0/G1 phase of the cell-cycle. The data indicates that acrolein enhances HO-1 expression via PKC-δ and p38 MAPK signaling. Acrolein may provide a cytoprotective effect via the expression of HO-1 in HepG2 cells.