Nicotine Promotes Cardiomyocyte Apoptosis via Oxidative Stress and Altered Apoptosis-Related Gene Expression

Abstract

Objective: To investigate the effect of nicotine on cardiomyocyte apoptosis in vitro and explore the potential mechanisms involved. Methods: The MTT assay was used to detect the viability of cultured cardiomyocytes exposed to different concentrations of nicotine (0.1–100 µM). Laser confocal microscopy, TUNEL assay and flow cytometry were utilized to detect cardiomyocyte apoptosis. Oxidative stress was evaluated by the levels of lactic dehydrogenase, malondialdehyde and superoxide dismutase in the supernatant of culture media. Real-time PCR was conducted to identify mRNA expression changes in apoptosis-related genes between the nicotine and the control group. Results: Nicotine was found to inhibit cardiomyocyte viability in a concentration-dependent manner. Our results demonstrated that nicotine can promote cardiomyocyte apoptosis and the antioxidant glutathione can protect cardiomyocytes from apoptosis via inhibition of nicotine-induced oxidative stress. Real-time PCR indicated that the expression of Bcl-2, Pax3, Bmp4 and Slug was down-regulated in the nicotine group, while the expression of P53, Bax and Msx1 was up-regulated. Conclusion: Nicotine promotes cardiomyocyte apoptosis by inducing oxidative stress and disrupting apoptosis-related gene expression.

Cytotoxicity and apoptosis induction by e-cigarette fluids in human gingival fibroblasts

“…The nicotine seems to exert a time-dependent effect, while the nicotinefree fluid's toxicity may be milder because after 48 h, nicotine-free fluid-mediated Bax expression is similar to the control. On one hand, these results are in line with the one by Zhou et al [32] who demonstrated an up-regulation of Bax gene expression in cardiomyocytes treated with nicotine; on the other hand, a toxicity, such as the up-regulation of a proapoptotic protein, ascribable to the fluid itself, could be confirmed. Last, we investigated the apoptosis and necrosis induction, finding an effect after late experimental times.…”

Effects of nicotine on proliferation and osteoblast differentiation in human alveolar bone marrow-derived mesenchymal stem cells

“…However, since treatment with 5 mM nicotine over 5 days induced extensive cell death, we ruled out the concentration from the osteoblast differentiation-related experiments in this study. Several studies have indicated that nicotine can induce necrosis in a variety of cells (Liu et al, 2005;Wickenden et al, 2003) and can induce apoptosis (Zhou et al, 2010). These results suggest that the effect of nicotine on cell death is dependent on the cell type.…”

Chronic nicotine exposure augments renal oxidative stress and injury through transcriptional activation of p66shc

“…We and others have shown that the activity of the p66shc promoter is activated by p53 [25,26] and hypomethylation [27,28]. It is important to note that smoking/NIC increases the expression of p53 mRNA in cardiomyocytes [33], fibroblasts [34] and certain regions of the brain [35], and inhibits the activity of DNA methyltransferase 1 [36]. We also noted that the expression of p53 is higher in the Ch-NICexposed kidneys (data not shown) and that the DNA methyltransferase inhibitor 5AZA increases basal and H 2 O 2 -dependent activation of the p66shc promoter [28].…”