Acrolein, an Environmental Toxin, Induces Cardiomyocyte Apoptosis via Elevated Intracellular Calcium and Free Radicals

Abstract

Acrolein, an unsaturated aldehyde, is an environmental toxin known to inhibit mitochondrial electron transport chain in brain and induce lipid peroxidation and apoptosis. However, the nature of the effects of acrolein on cardiac function and myocardium is not known. The objective of this study is to examine whether acrolein induces apoptosis in cardiomyocytes and alters cytosolic calcium concentration and the intracellular oxygen free-radical levels. Adult mouse cardiomyocytes exposed to 1 μmol/l of acrolein showed a marked increase in the intracellular oxygen free-radicals and calcium concentration, by 12- and 2-fold, respectively, compared to the resting value. Moreover, the cardiomyocyte viability decreased significantly in a dose-dependent manner by treatment with 25, 50, and 100 μmol/l of acrolein compared to controls. Morphological changes and DNA laddering typical of apoptosis were found in acrolein-exposed cardiomyocytes. Our finding suggested that acrolein caused apoptotic death of adult mice cardiomyocytes by increasing intracellular oxygen free-radicals and calcium concentration.

The Uremic Toxin Acrolein Promotes Suicidal Erythrocyte Death

“…the stimulation of erythrocyte cell membrane scrambling, a typical feature of suicidal death or eryptosis. The concentrations of acrolein required for statistically significant stimulation of cell membrane scrambling (30 µM) are similar to those (25 -100 µM) previously shown to trigger death of nucleated cells [57,58]. …”

“…In nucleated cells acrolein can induce both, necrotic and apoptotic cell death [52,57,58,59]. According to the present observations the extent of hemolysis is clearly smaller than the percentage of cell membrane scrambling suggesting that the erythrocytes die from eryptosis rather than hemolysis.…”

Lipid Peroxidation by-Products and the Metabolic Syndrome

“…However, an interesting paradigm was pointed out by several groups: lipid aldehydes are able to induce the production of ROS, and this is thought to be of importance in their deleterious effects. For instance, acrolein treatment produces nitric oxide (Misonou et al, 2006) and induces generation of intracellular oxidants (Luo et al, 2005;Wang et al, 2011). Similarly, accumulation of intracellular ROS was described in cells treated with MDA (Cheng et al, 2011); and unsurprisingly, the 4-hydroxyalkenals HHE and HNE share the same ability.…”

Acrolein-induced inflammatory signaling in vascular smooth muscle cells requires activation of serum response factor (SRF) and NFκB

“…Therefore, it is possible that SRF may be involved in acrolein-induced tissue injury through alteration of pathways involved in VSMC growth and differentiation. Generation of ROS, increased intracellular calcium level and damage to SMCs have been proposed as some of the mechanisms behind acrolein toxicity [50,51] . Because it has been well established that both ROS and increased intracellular calcium can up-regulate SRF [52,53] , it is not surprising to see increased SRF expression in acrolein toxicity.…”