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The coffee diterpene kahweol induces heme oxygenase‐1 via the PI3K and p38/Nrf2 pathway to protect human dopaminergic neurons from 6‐hydroxydopamine‐derived oxidative stress
Author(s) -
Hwang Yong Pil,
Jeong Hye Gwang
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2008.06.045
Subject(s) - neuroprotection , hydroxydopamine , heme oxygenase , oxidative stress , neurotoxin , chemistry , heme , p38 mitogen activated protein kinases , pi3k/akt/mtor pathway , intracellular , pharmacology , biochemistry , signal transduction , microbiology and biotechnology , dopaminergic , biology , enzyme , dopamine , mapk/erk pathway , neuroscience
In this study, we investigated the mechanisms of kahweol protection of neuronal cells from cell death induced by the Parkinson's disease‐related neurotoxin 6‐hydroxydopamine (6‐OHDA). Pretreatment of SH‐SY5Y cells with kahweol significantly reduced 6‐OHDA‐induced generation of ROS, caspase‐3 activation, and subsequent cell death. Kahweol also up‐regulated heme oxygenase‐1 (HO‐1) expression, which conferred neuroprotection against 6‐OHDA‐induced oxidative injury. Moreover, kahweol induced PI3K and p38 activation, which are involved in the induction of Nrf2, HO‐1 expression, and neuroprotection. These results suggest that regulation of the anti‐oxidant enzyme HO‐1 via the PI3K and p38/Nrf2 signaling pathways controls the intracellular levels of ROS.