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Resveratrol Protects Dopaminergic Neurons in Parkinson's Disease Models by Modulating the PKC‐delta Apoptotic Signaling Pathway & Microglial Activation
Author(s) -
Gordon Richard,
Hogan Colleen Elizabeth,
Kanthasamy Kavin,
Vellareddy Anantharam,
Kanthasamy Arthi,
Kanthasamy Anumantha G
Publication year - 2010
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.24.1_supplement.763.5
Subject(s) - resveratrol , neurodegeneration , neuroprotection , microglia , dopaminergic , microbiology and biotechnology , chemistry , signal transduction , pharmacology , viability assay , apoptosis , biology , inflammation , neuroscience , biochemistry , dopamine , immunology , medicine , disease
Resveratrol is a phytoalexin that has been shown to be neuroprotective in various models of neurodegeneration. Although resveratrol is recognized as a potent antioxidant, emerging evidence suggests this compound can exert its protective function by modulating various signaling pathways including SIRT‐1, NF‐κB, and various kinases. Recent studies from our lab demonstrated that protein kinase Cδ (PKCδ) is an oxidative stress sensitive kinase that is proteolytically activated to induce apoptotic cell death in Parkinson's disease (PD) models. In this study, we examined whether i) resveratrol protects against dopaminergic neurodegeneration in cell culture models of PD ii) resveratrol modulates the PKCδ dependent apoptotic cascade in dopaminergic neuronal cells and iii) resveratrol can suppress the inflammatory response in activated microglia. Resveratrol treatment significantly increased cell viability and attenuated MPP + ‐induced DNA fragmentation and caspase‐3 activity in mesencephalic dopaminergic neuronal cells (N27 cells). We also observed that resveratrol effectively blocked the proteolytic cleavage of PKCδ and kinase activity induced by MPP + treatment. We further confirmed the protective effect of resveratrol in MPP + treated primary mesencephalic neuron cultures. In BV‐2 microglial cells activated with LPS, pretreatment with resveratrol suppressed pro‐inflammatory cytokine production and nitric oxide release. Collectively, our results demonstrate that resveratrol protects against the degenerative process in dopaminergic neurons by modulating the PKCδ proapoptotic signaling pathway and can also attenuate the inflammatory response in activated microglia