[PP.36.07] MODIFICATION OF HISTONE INDUCED BY ACROLEIN IN RAT VASCULAR SMOOTH MUSCLE CELLS

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Abstract

Objective:

Modifications of histones due to environmental pollutants have been reported to affect chromatin structure and ultimately play an important role in the regulation of gene expression. Several studies have shown that these modifications are associated with cardiac problems during development and differentiation. Acrolein, an environmental pollutant and a major component of cigarette smoke, has been implicated in cardiovascular toxicity and several neurological disorders such as Alzheimer's disease. N-acetyl cysteine (NAC), an antioxidant, has been reported to prevent acrolein toxicity. The goal of the present study was to investigate whether or not exposure to sub-toxic levels of acrolein causes epigenetic alterations in rat's vascular smooth muscle cells (VSMCs) and if the protection by NAC is related to these changes.

Design and method:

VSMCs were treated with 2 and 3 μg/ml of acrolein for 1, 6 and 18 hours in the present or absent of 10 mM NAC. At the end of the treatment, cells were checked for viability. Additionally, immunofluorescence staining was used to analysis H3Lys9 acetylation and H3Ser10 phosphorylation. Western blot analysis was used to determine H3K4, H3K9, H3K27 and H4K20 tri-methylation and H3K9 and H3K56 acetylation.

Results:

Cells treated with 2 and 3 μg/ml of acrolein did not exhibit any toxicity for the different time points. Acrolein exposed VSMC displayed induction of histone H3-lysine9 and 56 acetylation (30% & 35% respectively) and reduced H3-lysine9 tri-methylation (25% respectively). Co-treated VSMCs with acrolein and N-acetyl cysteine, exhibited reduced H3-lysine9 acetylation, induced H3-Serine10 phosphorylation and di-methylation (26% & 31% respectively) and reduced H3-Lysine4 di-methylation (22%).

Conclusions:

Based on these data we are concluding that exposure to sub-toxic levels of acrolein results in alterations in DNA methylation and histone lysine methylation and acetylation which can be prevented with addition of NAC.

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