The Journal of Toxicological Sciences
Online ISSN : 1880-3989
Print ISSN : 0388-1350
ISSN-L : 0388-1350
Original Article
Crotonaldehyde induces apoptosis in alveolar macrophages through intracellular calcium, mitochondria and p53 signaling pathways
Bi-cheng YangXiu-jie PanZhi-hua YangFeng-jun XiaoXing-yu LiuMao-xiang ZhuJian-ping Xie
Author information

2013 Volume 38 Issue 2 Pages 225-235


Crotonaldehyde, a highly electrophilic α, β-unsaturated aldehyde, is a ubiquitous environmental pollutant and a risk factor for multiple respiratory diseases. Crotonaldehyde is highly volatile and hydrophilic, so it is efficiently absorbed in the respiratory tract. Alveolar macrophages are major effector cells of the nonspecific host defence in the lung. The aim of this study was to investigate the molecular mechanisms and signaling pathways responsible for cell death of alveolar macrophage induced by crotonaldehyde. Our results show that crotonaldehyde induces apoptosis in alveolar macrophages, as indicated by phosphatidylserine externalization and DNA fragmentation. Pretreatment of alveolar macrophages with N-acetylcysteine, ascorbic acid, α-tocopherol, superoxide dismutase inhibited crotonaldehyde-induced apoptosis. Crotonaldehyde-induced apoptosis was characterized by ROS generation, GSH depletion, loss of mitochondrial membrane potential (ΔΨm), the release of cytochrome c from mitochondria, caspase-3/7 and caspase-9 activation, elevation of intracellular Ca2+ concentration and the increase of p53 expression. Furthermore, pretreatment with either p53 inhibitor pifithrin-α or calcium chelator BAPTA-AM effectively attenuated apoptosis induced by crotonaldehyde. Taken together, our results showed that crotonaldehyde induce apoptosis in alveolar macrophages through intracellular calcium, mitochondria and p53 signaling pathways. These results would help to illustrate the mechanism of toxicity induced by crotonaldehyde and to look for a novel treatment for diseases induced by exposure to crotonaldehyde-rich pollutants such as cigarette smoke.

Content from these authors
© 2013 The Japanese Society of Toxicology
Previous article Next article