Homocysteine and copper induce cellular apoptosis via caspase activation and nuclear translocation of apoptosis-inducing factor in neuronal cell line SH-SY5Y

Hyperhomocysteinemia has been implicated in dementia and neurodegenerative disease. Physiological homocysteine concentrations did not result in apoptosis in SH-SY5Y cells in the present study. The apoptosis was recognized in millimolar level of homocysteine. However, SH-SY5Y cell death was observed...

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Published inNeuroscience research Vol. 67; no. 4; pp. 300 - 306
Main Authors Hirashima, Yoshimasa, Seshimo, So, Fujiki, Yoshika, Okabe, Masaaki, Nishiyama, Kazuo, Matsumoto, Mitsuharu, Kanouchi, Hiroaki, Oka, Tatsuzo
Format Journal Article
LanguageEnglish
Published Ireland Elsevier Ireland Ltd 01.08.2010
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Summary:Hyperhomocysteinemia has been implicated in dementia and neurodegenerative disease. Physiological homocysteine concentrations did not result in apoptosis in SH-SY5Y cells in the present study. The apoptosis was recognized in millimolar level of homocysteine. However, SH-SY5Y cell death was observed following exposure to micromolar level of homocysteine in combination with copper. Exposure to 250 μM homocysteine and 10 μM CuCl 2 for one day decreased cell viability by 40%. Homocysteine and copper caused apoptosis, because hallmarks of apoptosis were recognized, such as loss of mitochondrial membrane potential, TUNEL-positive cells, release of cytochrome c from mitochondria, and caspase-3 activation, but not nucleosomal DNA fragmentation. Homocysteine and copper generated the intracellular reactive oxygen species, and homocysteine and copper-induced apoptosis was due to an accumulation of intracellular reactive oxygen species, which was inhibited by catalase. Pan-caspase inhibitor, z-VAD-fmk, could not completely inhibited homocysteine and copper-induced cell death. Homocysteine and copper also caused the nuclear translocation of apoptosis-inducing factor. These results suggested that homocysteine and copper induced not only caspase-dependent apoptosis but also caspase-independent apoptosis-inducing factor related apoptosis.
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ISSN:0168-0102
1872-8111
DOI:10.1016/j.neures.2010.04.013