Protective effect of isoflavones against homocysteine-mediated neuronal degeneration in SH-SY5Y cells.
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.
Park
Youn-Jin
YJ
Department of Food and Nutrition, Seoul National University, San 56-1 Sillim-Dong, Kwanak-Gu, Seoul, 151-742, Korea.
Jang
Yumi
Y
Kwon
Young Hye
YH
D000544:Alzheimer Disease / Q000188:drug therapy* / Q000473:pathology* / Q000503:physiopathology; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D004721:Endoplasmic Reticulum / Q000187:drug effects / Q000378:metabolism; D006710:Homocysteine / Q000633:toxicity*; D006801:Humans; D007529:Isoflavones / Q000494:pharmacology*; D009410:Nerve Degeneration; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D020011:Protective Agents / Q000494:pharmacology*; D012435:S-Adenosylhomocysteine / Q000378:metabolism
D007529:Isoflavones; D020011:Protective Agents; D006710:Homocysteine; D012435:S-Adenosylhomocysteine