Autophagy in Crotonaldehyde-Induced Endothelial Toxicity

Abstract

Crotonaldehyde is an extremely toxic α,β-unsaturated aldehyde found in cigarette smoke, and it causes inflammation and vascular dysfunction. Autophagy has been reported to play a key role in the pathogenesis of vascular diseases. However, the precise mechanism underlying the role of acute exposure crotonaldehyde in vascular disease development remains unclear. In the present study, we aimed to investigate the effect of crotonaldehyde-induced autophagy in endothelial cells. Acute exposure to crotonaldehyde decreased cell viability and induced autophagy followed by cell death. In addition, inhibiting the autophagic flux markedly promoted the viability of endothelial cells exposed to high concentrations of crotonaldehyde. Crotonaldehyde activated the AMP-activated protein kinase (AMPK) and p38 mitogen-activated protein kinase (MAPK) pathways, and pretreatment with inhibitors specific to these kinases showed autophagy inhibition and partial improvement in cell viability. These data show that acute exposure to high concentrations of crotonaldehyde induces autophagy-mediated cell death. These results might be helpful to elucidate the mechanisms underlying crotonaldehyde toxicity in the vascular system and contribute to environmental risk assessment.

Proteomics-based evaluation of the mechanism underlying vascular injury via DNA interstrand crosslinks, glutathione perturbation, mitogen-activated protein kinase, and Wnt and ErbB signaling pathways induced by crotonaldehyde

“…These indicators strongly suggest that CRA is associated with arterial dysfunction and structural changes in the vasculature. One study confirmed that acute exposure to high concentrations of CRA induces arterial dysfunction and structural changes in the vasculature through activated MAPK pathways [ 45 ]. Meanwhile, we confirmed that the activation of MAPK pathways can directly induce structural changes and arterial dysfunction in the vasculature with low concentrations of CRA (Fig.…”

Advances in the molecular regulation mechanism of tumor dormancy and its therapeutic strategy

“…Autophagy, a cellular process involving lysosome-mediated degradation, is pivotal for protein breakdown, cytoplasmic organelle renewal, and recycling of cellular components [ 80 ]. Four functions of autophagy, cytoprotective, nonprotective, cytotoxic, and cytostatic, have been reported in the existing literature [ 81 ].…”