期刊
MOLECULAR AND CELLULAR BIOCHEMISTRY
卷 283, 期 1-2, 页码 115-122出版社
SPRINGER
DOI: 10.1007/s11010-006-2386-3
关键词
antioxidants; apoptosis; calcineurin; cardiomyocytes; eugenol; oxidative stress
类别
In view of the known involvement of oxidative stress and calcineurin (Ca2+-calmodulin dependent protein phosphatase) in beta-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 mu M 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 mu M 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.
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