Effect of crotonaldehyde on the induction of HO-1 expression in A549 cells

Abstract

Cigarette smoke contains approximately 5,000 chemical components, including reactive chemicals and free radicals that are associated with an increased risk of chronic obstructive pulmonary disease (COPD). Cigarette smoke is also known to promote inflammation as part of various inflammatory airway diseases. Crotonaldehyde (CRA) is a highly toxic α, β-unsaturated aldehyde that is a major component of cigarette smoke. Exposure to CRA has been previously shown to result in adverse effects on respiratory health. Heme oxygenase-1 (HO-1) is an inducible enzyme that is activated by various stress-inducing stimuli to perform a diverse range of physiological functions, including anti-oxidant, anti-apoptotic, and anti-inflammatory effects. The present study aimed to investigate the effect of CRA stimulation on HO-1 expression in human lung adenocarcinoma epithelial (A549) cells. Stimulation of cells with CRA was shown to result in upregulated HO-1 expression via the induction of nuclear factor erythroid 2-related factor 2 (Nrf2) nuclear translocation, and activation of the p38 mitogen-activated protein kinase (MAPK) pathway. Furthermore, zinc protoporphyrin (ZnPP; a specific HO-1 inhibitor) was used to inhibit HO-1 activity, and this was shown to cause a significant increase in the rate of apoptosis of CRA-exposed cells. Taken together, these results suggest that HO-1 exerts an anti-apoptotic effect in CRA-exposed human lung adenocarcinoma epithelial cells, and thus protects cells against CRA-induced oxidative stress.