Nicotine promotes cardiomyocyte apoptosis via oxidative stress and altered apoptosis-related gene expression

Cardiology. 2010;115(4):243-50. doi: 10.1159/000301278. Epub 2010 Mar 26.

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 microM). 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Bone Morphogenetic Protein 4 / genetics
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cells, Cultured
  • Gene Expression / drug effects
  • Gene Expression / physiology
  • In Situ Nick-End Labeling
  • MSX1 Transcription Factor / genetics
  • Myocytes, Cardiac* / cytology
  • Myocytes, Cardiac* / drug effects
  • Myocytes, Cardiac* / metabolism
  • Nicotine / pharmacology*
  • Nicotinic Agonists / pharmacology*
  • Oxidative Stress / drug effects
  • Oxidative Stress / physiology
  • PAX3 Transcription Factor
  • Paired Box Transcription Factors / genetics
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Rats
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Snail Family Transcription Factors
  • Transcription Factors / genetics
  • Tumor Suppressor Protein p53 / genetics
  • bcl-2-Associated X Protein / genetics

Substances

  • Bax protein, rat
  • Bmp4 protein, rat
  • Bone Morphogenetic Protein 4
  • MSX1 Transcription Factor
  • Msx1 protein, rat
  • Nicotinic Agonists
  • PAX3 Transcription Factor
  • PAX3 protein, rat
  • Paired Box Transcription Factors
  • Proto-Oncogene Proteins c-bcl-2
  • Snai2 protein, rat
  • Snail Family Transcription Factors
  • Transcription Factors
  • Tumor Suppressor Protein p53
  • bcl-2-Associated X Protein
  • Nicotine