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Protective effect of isoflavones against homocysteine-mediated neuronal degeneration in SH-SY5Y cells

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Abstract

Previously, we reported that isoflavones exert a protective effect against the endoplasmic reticulum (ER) stress-mediated neuronal degeneration, and ER stress-mediated homocysteine toxicity may play an important role in the pathogenesis of neurodegeneration. Therefore, in this study we investigated the effects of isoflavones (genistein and daidzein) against homocysteine-mediated neurotoxicity in SH-SY5Y human neuroblastoma cells. The treatment of cells with either 17β-estradiol or isoflavones significantly protected the cells against homocysteine-mediated apoptosis. Isoflavones repressed homocysteine-mediated ER stress, reflected in the reduced expression of the immunoglobin heavy chain-binding protein mRNA, spliced X-box-protein-1 mRNA and the phosphorylated form of eukaryotic translation initiation factor 2α protein. Homocysteine caused significant increases in intracellular S-adenosylhomocysteine (SAH) and DNA damage. Isoflavones significantly alleviated DNA damage, but did not change SAH levels. Furthermore, the treatment of cells with isoflavones significantly reduced the microtubule-associated protein tau hyperphosphorylation by inactivating glycogen synthase kinase-3β and activating serine/threonine-protein phosphatase 2A. These results clearly demonstrate that isoflavones alleviate the ER stress- and DNA damage-mediated neurodegeneration caused by homocysteine.

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Acknowledgments

This work was supported by a grant from the Korea Research Foundation (KRF-2006-331-C00311), Korea.

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Authors and Affiliations

  1. Department of Food and Nutrition, Seoul National University, San 56-1 Sillim-Dong, Kwanak-Gu, Seoul, 151-742, Korea

    Youn-Jin Park, Yumi Jang & Young Hye Kwon

  2. Research Institute of Human Ecology, Seoul National University, Seoul, Korea

    Young Hye Kwon

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  1. Youn-Jin Park
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  2. Yumi Jang
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Correspondence to Young Hye Kwon.

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Park, YJ., Jang, Y. & Kwon, Y.H. Protective effect of isoflavones against homocysteine-mediated neuronal degeneration in SH-SY5Y cells. Amino Acids 39, 785–794 (2010). https://doi.org/10.1007/s00726-010-0523-5

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