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Abstract Title:

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

Abstract Source:

Amino Acids. 2010 Aug;39(3):785-94. Epub 2010 Mar 4. PMID: 20204436

Abstract Author(s):

Youn-Jin Park, Yumi Jang, Young Hye Kwon

Article Affiliation:

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

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 17beta-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 2alpha 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-3beta 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.

Study Type : In Vitro Study

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