Sulforaphane protects against 6-hydroxydopamine-induced cytotoxicity             by increasing expression of heme oxygenase-1 in a PI3K/Akt-dependent manner.
Parkinson's disease (PD) is a progressive neurodegenerative disorder with             selective loss of dopaminergic neurons in the substantia nigra. Evidence suggests             that oxidative stress is involved in the pathogenesis of PD. Sulforaphane (SF),             a naturally occurring isothiocyanate, has been shown to protect against oxidative             stress by inducing the expression of various NF-E2-related factor-2 (Nrf2) responsive             genes. Previous studies have shown that SF protects dopaminergic neurons against             PD-related neurotoxin 6-hydroxydopamine (6-OHDA)-induced cytotoxicity. However,             the molecular mechanisms by which SF protects against 6-OHDA-induced cytotoxicity             are poorly elucidated. In this study, we found that pretreatment with SF significantly             reduced 6-OHDA-induced caspase-3 activation and subsequent cell death. SF also             increased heme oxygenase-1 (HO-1) expression, which conferred protection against             6-OHDA-induced cytotoxicity. Furthermore, SF induced the translocation of Nrf2             into the nucleus and activated PI3K/Akt, a pathway that is involved in SF-induced             Nrf2 nuclear translocation, HO-1 expression and cytoprotection. These results             suggest that SF inhibits 6-OHDA-induced cytotoxicity through increasing HO-1 expression             in a PI3K/Akt-dependent manner.
Department of Emergency, The People's Hospital of Guang Du District, Kunming 650200, PR China.
Chang
C
Deng
Ran
R
Tao
Shun-Zhi
SZ
Yu
Hua
H
Jin
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects*; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D016627:Oxidopamine / Q000633:toxicity*; D016716:PC12 Cells; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*; D051381:Rats; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology*
D016588:Anticarcinogenic Agents; D053148:Caspase 3; D051547:Heme Oxygenase-1; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D016627:Oxidopamine; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D013454:Sulfoxides; D013861:Thiocyanates; C016766:sulforaphane