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Mitochondria are important sensor of apoptosis. $H_2O_2-induced$ cell death rate was enhanced by serum deprivation. In this study, we investigated whether serum deprivation using 0.5 or 3 % FBS induces apoptotic cell death through mitochondrial enzyme activation as compared to 10 % FBS. Apoptotic cell death was observed by chromosome condensation and the increase of sub-G0/G1 population. Serum deprivation reduced cell growth rate, which was confirmed by the decrease of S-phase population in cell cycle. Serum deprivation significantly increased caspase-9 activity and cytochrome c release from mitochondria into cytosol. Serum deprivation-induced mitochondrial changes were also indicated by the increase of ROS production and the activation of mitochondrial enzyme, succinate dehydrogenase. Mitochondrial enzyme activity increased by serum deprivation was reduced by the treatment with rotenone, mitochondrial electron transport inhibitor. In conclusion, serum deprivation induced mitochondrial apoptotic cell death through the elevation of mitochondrial changes such as ROS production, cytochrome c release and caspase-9 activation. It suggests that drug sensitivity could be enhanced by the increase of mitochondrial enzyme activity in serum-deprived condition.
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참고문헌 (29)
참고문헌 신청
Bialik, S / 1999 / The mitochondrial apoptotic pathway is activated by serum and glucose deprivation in cardiac myocytes / Circ. Res 85:403~414
Chance, B / 1963 / Inhibition of electron and energy transfer in mitochondria. I. Effects of Amytal, thiopental, rotenone, progesterone, and methylene glycol / J Biol. Chem 238:418~431
Colombaioni, L / 2002 / Role of mitochondria in serum withdrawal-induced apoptosis of immortalized neuronal precursors / Brain Res. Dev. Brain Res 134:93~102
Colombaioni, L / 2002 / Serum deprivation increases ceramide levels and induces apoptosis in undifferentiated HN9.10e cells / Neurochem. Int 40:327~336
Denizot, F / 1986 / Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability / J. Immunol. Methods 89:271~277
Chance, B / 1963 / Inhibition of electron and energy transfer in mitochondria. I. Effects of Amytal, thiopental, rotenone, progesterone, and methylene glycol / J Biol. Chem 238:418~431
Colombaioni, L / 2002 / Role of mitochondria in serum withdrawal-induced apoptosis of immortalized neuronal precursors / Brain Res. Dev. Brain Res 134:93~102
Colombaioni, L / 2002 / Serum deprivation increases ceramide levels and induces apoptosis in undifferentiated HN9.10e cells / Neurochem. Int 40:327~336
Denizot, F / 1986 / Rapid colorimetric assay for cell growth and survival. Modifications to the tetrazolium dye procedure giving improved sensitivity and reliability / J. Immunol. Methods 89:271~277
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