Interrelations between oxidative stress and calcineurin in the attenuation of cardiac apoptosis by eugenol

Rashmi Choudhary, Kaushala Prasad Mishra, Chivukula Subramanyam

Research output: Contribution to journalArticlepeer-review

Abstract

In view of the known involvement of oxidative stress and calcineurin (Ca2+-calmodulin dependent protein phosphatase) in β-Adrenergic stimulated events, we examined the influence of eugenol (an antioxidant generally regarded as safe by the Food and Agricultural Organization of the United Nations) on isoproterenol-induced apoptosis in neonatal cardiomyocytes. In comparison to unstimulated controls, cardiomyocytes stimulated with 50 μM isoproterenol for 48 h demonstrated (a) increased intracellular Ca2+ levels (b) oxidative stress involving enhanced reactive oxygen species, decreased GSH/GSSG ratio, enhanced lipid peroxidation, increased activities of superoxide dismutase and glutathione peroxidase (c) apoptosis, evidenced by increased number of annexin V/TUNEL positive cells, enhanced membrane fluidity, decreased mitochondrial membrane potential, increased activities of caspase 3 and 9 along with (d) increased calcineurin activity. Pre-incubation of cardiomyocytes with 100 μM eugenol for 1 h, followed by isoproterenol treatment for 48 h, led to reversal of enhanced intracellular Ca2+ levels, oxidative stress, calcineurin activation and apoptosis caused by isoproterenol. In addition, similar treatment of cardiomyocytes with 10 nM FK506, a calcineurin inhibitor, could also attenuate isoproterenol-induced apoptosis. These results indicate the beneficial effects of eugenol in preventing cardiomyocyte apoptosis.

Original languageEnglish (US)
Pages (from-to)115-122
Number of pages8
JournalMolecular and Cellular Biochemistry
Volume283
Issue number1-2
DOIs
StatePublished - Feb 1 2006

Keywords

  • Antioxidants
  • Apoptosis
  • Calcineurin
  • Cardiomyocytes
  • Eugenol
  • Oxidative stress

ASJC Scopus subject areas

  • Molecular Biology
  • Clinical Biochemistry
  • Cell Biology

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