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Role of induction of the 26S proteasome in protective effects of sulforaphane against hydrogen peroxide‐mediated cytotoxicity in murine neuroblastoma cells
Author(s) -
Kwak MiKyoung,
Cho Jeong Min,
Huang Bo,
Kensler Thomas W
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1175-b
Subject(s) - sulforaphane , proteasome , oxidative stress , chemistry , hydrogen peroxide , cytotoxicity , transfection , antioxidant , microbiology and biotechnology , biochemistry , in vitro , biology , gene
The 26S proteasome is responsible for degradation of cellular abnormal proteins and may play a role in cell survival upon oxidative stress. Indirect antioxidant sulforaphane found to protect animal tissues from chemical toxicants by increasing Nrf2‐regulated antioxidative genes. Cytoprotective effects of sulforaphane through an induction of the 26S proteasome were investigated in murine neuroblastoma Neuro2A cells. Sulforaphane enhanced expression of catalytic subunits of the proteasome, as well as proteasomal peptidase activities in these cells. Treatment with sulforaphane protected cells from cytotoxicity mediated by hydrogen peroxide and these protective effects were proteasomal function dependent. Inhibition of proteasome activities using pharmacological interventions significantly attenuated protective effects of sulforaphane against hydrogen peroxide, as well as reductive effects against hydrogen peroxide induced protein oxidation. While, enhanced proteasome function obtained by overexpressing the catalytic subunit PSMB5 demonstrated an elevated resistance against hydrogen peroxide treatment with reduced levels of oxidized proteins compared to those in blank plasmid transfected cells. Collectively, these results are suggesting that cytoprotective effects of sulforaphane against oxidative stress are in part due to an induction of the proteasome system. Therefore, application of proteasome inducers may provide a potential benefit in preventing oxidative stress associated damages in neuronal cells.