Activation of cellular signalling pathways and apoptosis by the aldehyde acrolein – A major environmental hazard

Abstract

Interest in the molecular actions of acrolein has increased in light of growing knowledge that implicates this reactive aldehyde in a wide range of pathophysiologies including neurodegenerative diseases, various lung disorders including chronic obstructive pulmonary disease, atherosclerosis, and certain cancers. This is rendered complex because acrolein exists in mixtures of environmental pollutants. Reactive α,β-unsaturated aldehydes like acrolein are major components of common environmental pollutants like cigarettes, automobile exhaust, and smoke from wood, coal, forest and house fires. It is a natural constituent of several foods and is generated in the human body during inflammation or oxidation of unsaturated lipids. Acrolein is also a toxic metabolic product of the widely used anticancer drug cyclophosphamide and is generated from the enzymatic oxidation of polyamines. It is a toxic by-product of lipid peroxidation and has been implicated as a mediator of oxidative damage in cells and tissues. The purpose of this review is to assess the literature about the activation of cell signalling pathways and transcription factors, and cell survival and cell death pathways by acrolein. Several reports show that anti-apoptosis processes dominate at lower dose exposures to acrolein, whereas pro-apoptotic processes and necrosis dominate at higher dose exposures. There has been improved understanding about the deleterious molecular and cellular mechanisms that are triggered in cells in response to acrolein injury. However, more progress is required to define the contributions of acrolein to human diseases and to design efficient therapeutic strategies based on the biochemical modulation of acrolein activity.