1. Sulforaphane protects against cytokine- and streptozotocin-induced β-cell damage by suppressing the NF-κB pathway
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Song, Mi-Young, Kim, Eun-Kyung, Moon, Woo-Sung, Park, Jin-Woo, Kim, Hyung-Jin, So, Hong-Seob, Park, Raekil, Kwon, Kang-Beom, and Park, Byung-Hyun
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STREPTOZOTOCIN , *ANTIOXIDANTS , *ENZYMES , *GENE expression , *CYTOKINES , *NITRIC-oxide synthases , *GLUTATHIONE transferase - Abstract
Abstract: Sulforaphane (SFN) is an indirect antioxidant that protects animal tissues from chemical or biological insults by stimulating the expression of several NF-E2-related factor-2 (Nrf2)-regulated phase 2 enzymes. Treatment of RINm5F insulinoma cells with SFN increases Nrf2 nuclear translocation and expression of phase 2 enzymes. In this study, we investigated whether the activation of Nrf2 by SFN treatment or ectopic overexpression of Nrf2 inhibited cytokine-induced β-cell damage. Treatment of RIN cells with IL-1β and IFN-γ induced β-cell damage through a NF-κB-dependent signaling pathway. Activation of Nrf2 by treatment with SFN and induction of Nrf2 overexpression by transfection with Nrf2 prevented cytokine toxicity. The mechanism by which Nrf2 activation inhibited NF-κB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H2O2 production. The protective effect of SFN was further demonstrated by the restoration of normal insulin secreting responses to glucose in cytokine-treated rat pancreatic islets. Furthermore, pretreatment with SFN blocked the development of type 1 diabetes in streptozotocin-treated mice. [Copyright &y& Elsevier]
- Published
- 2009
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