Sulforaphane protects against cytokine- and streptozotocin-induced beta-cell damage by suppressing the NF-kappaB pathway.
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 beta-cell damage. Treatment of RIN cells with IL-1beta and IFN-gamma induced beta-cell damage through a NF-kappaB-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-kappaB-dependent cell death signals appeared to involve the reduction of oxidative stress, as demonstrated by the inhibition of cytokine-induced H(2)O(2) 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.
Song
Mi-Young
MY
Department of Biochemistry, Medical School and Diabetes Research Center, Chonbuk National University, Jeonju, Jeonbuk, 561-756, Republic of Korea.
Kim
Eun-Kyung
EK
Moon
Woo-Sung
WS
Park
Jin-Woo
JW
Kim
Hyung-Jin
HJ
So
Hong-Seob
HS
Park
Raekil
R
Kwon
Kang-Beom
KB
Park
Byung-Hyun
BH
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000517:prevention & control; D003922:Diabetes Mellitus, Type 1 / Q000139:chemically induced / Q000517:prevention & control; D005947:Glucose / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects*; D017879:Isothiocyanates; D008297:Male; D051379:Mice; D008813:Mice, Inbred ICR; D016328:NF-kappa B / Q000378:metabolism*; D009569:Nitric Oxide; D051381:Rats; D017207:Rats, Sprague-Dawley; D013047:Specific Pathogen-Free Organisms; D013311:Streptozocin / Q000633:toxicity*; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016207:Cytokines; D007328:Insulin; D017879:Isothiocyanates; D016328:NF-kappa B; D013454:Sulfoxides; D013861:Thiocyanates; D009569:Nitric Oxide; D013311:Streptozocin; C016766:sulforaphane; D005947:Glucose