title: Homocysteine induced SH-SY5Y apoptosis through activation of NADPH oxidase in U251MG cells.
abstract: Epidemiological studies have indicated a correlation between homocysteinemia and dementia, including Alzheimer's disease. However, the mechanism by which homocysteine (Hcy) induces neuronal cell death remains unknown. We found that micromolar concentrations of Hcy induced neuroblastoma SH-SY5Y cell death only when co-cultured with glioblastoma U251MG cells. In this culture system, cysteine had no effect on SH-SY5Y cell death. There was an increase in TUNEL-positive cells and loss of mitochondrial membrane potential following treatment with 100 μM Hcy. Addition of conditioned medium prepared from U251MG cells in the presence of 100 μM Hcy also reduced SH-SY5Y cell viability, while this effect was prevented when using conditioned medium from U251MG cells exposed to 100 μM Hcy+apocynin, a specific NADPH oxidase inhibitor. Following exposure to 100 μM Hcy in U251MG cells, expression of Rac1, a compartment of NADPH oxidase, was translocated to the plasma membrane, and the active form of Rac1 was increased. There was no change in peroxide concentration in the medium of U251MG cells after addition of Hcy. Overall, these data suggest that Hcy stimulates Rac1 activation and NADPH oxidase, resulting in superoxide anion production that may induce SH-SY5Y cell apoptosis.
authors: Department of Veterinary Pathobiology, Faculty of Agriculture, Kagoshima University, 1-21-24 Korimoto, Kagoshima 890-0065, Japan.
authors: Yoshika
authors: Y
authors: Fujiki
authors: Yoshimasa
authors: Y
authors: Hirashima
authors: So
authors: S
authors: Seshimo
authors: Takeaki
authors: T
authors: Okamoto
authors: Yasushi
authors: Y
authors: Sugimoto
authors: Mitsuharu
authors: M
authors: Matsumoto
authors: Tatsuzo
authors: T
authors: Oka
authors: Hiroaki
authors: H
authors: Kanouchi
mesh_terms: D000098:Acetophenones / Q000494:pharmacology; D000199:Actins / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016923:Cell Death; D045744:Cell Line, Tumor; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D006710:Homocysteine / Q000494:pharmacology*; D006801:Humans; D053078:Membrane Potential, Mitochondrial / Q000187:drug effects / Q000502:physiology; D019255:NADPH Oxidases / Q000378:metabolism*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020830:rac1 GTP-Binding Protein / Q000378:metabolism
chemical_list: D000098:Acetophenones; D000199:Actins; D017382:Reactive Oxygen Species; D006710:Homocysteine; C056165:acetovanillone; D019255:NADPH Oxidases; D020830:rac1 GTP-Binding Protein