TY - JOUR
T1 - Interrelations between oxidative stress and calcineurin in the attenuation of cardiac apoptosis by eugenol
AU - Choudhary, Rashmi
AU - Mishra, Kaushala Prasad
AU - Subramanyam, Chivukula
PY - 2006/2/1
Y1 - 2006/2/1
N2 - 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.
AB - 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.
KW - Antioxidants
KW - Apoptosis
KW - Calcineurin
KW - Cardiomyocytes
KW - Eugenol
KW - Oxidative stress
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U2 - 10.1007/s11010-006-2386-3
DO - 10.1007/s11010-006-2386-3
M3 - Article
C2 - 16444593
AN - SCOPUS:33645771759
VL - 283
SP - 115
EP - 122
JO - Molecular and Cellular Biochemistry
JF - Molecular and Cellular Biochemistry
SN - 0300-8177
IS - 1-2
ER -