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P4‐181: Homocysteine, S‐adenosylmethionine/s‐adenosylhomocysteine ratio, glutathione and nitric oxide levels in TgCRDND8 mice fed with B vitamin‐deficient diet
Author(s) -
Cavallaro Rosaria A.,
Fuso Andrea,
Nicolia Vincenzina,
Scarpa Sigfrido
Publication year - 2008
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2008.05.2248
Subject(s) - hyperhomocysteinemia , glutathione , homocysteine , nitric oxide , transsulfuration , chemistry , oxidative stress , cystathionine beta synthase , methionine , cysteine , medicine , methylation , endocrinology , biochemistry , vitamin b12 , metabolism , biology , enzyme , amino acid , gene
the neuroprotective role of RSV in SK-N-BE, a neuroblastoma cell line that we challenged with oxidative stress, a common feature of neurodegenerative disorders. Cells were exposed to 75 M hydrogen peroxyde (H202) or 75 M 6-hydroxydopamine (6-OHDA) for 24 h, while sirtuins activity was increased by 7.5 M RSV addition. Moreover, cells were exposed to 10 M A (1-42) and 3 M -synuclein to trigger toxicity. Finally SIRT1 expression was downregulated by siRNA methodology and sirtuins activity was blocked by sirtinol. Results: We found that RSV was able to prevent cellular death triggered by hydrogen peroxyde and the dopaminergicselecive toxin 6-hydroxydopamine (6-OHDA). This action was independent from RSV antioxidant properties but was likely mediated by Sirt1 activation, as RSV protection was lost in presence of the Sirt1 inhibitor sirtinol and when SIRT1 expression was downregulated by siRNA approach. Moreover, we have confirmed that RSV was alsoable to prevent cellular damage due to the exposure to aggregation-prone proteins as amyloid -peptide (1-42) (A 42) and a mutated form of -synuclein [ -syn(A30P), exogenously added to cells by means of the fusion protein TAT-syn(A30P)]. RSV protection against TAT-syn toxicity was likely mediated by sirtuins activation, as it was prevented by sirtinol addition; however, sirtinol was not able to prevent RSV-mediated protection against A (1-42). Conclusions: Our data suggest that RSV might be a useful tool in preventing neurodegenerative processes triggered by oxidative stress or protein aggregation.