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Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C. Br J Pharmacol

Department of Psychiatry, Douglas Hospital Research Centre, McGill University, 6875 Boulevard LaSalle, Montreal, Québec, Canada H4H 1R3.
British Journal of Pharmacology (Impact Factor: 4.99). 04/2004; 141(6):997-1005. DOI: 10.1038/sj.bjp.0705688
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ABSTRACT 1. Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models. 2. The present study evaluated the neuroprotective effects of resveratrol against amyloid beta(Abeta)-induced toxicity in cultured rat hippocampal cells and examined the role of the protein kinase C (PKC) pathway in this effect. 3. Pre-, co- and post-treatment with resveratrol significantly attenuated Abeta-induced cell death in a concentration-dependent manner, with a concentration of 25 microm being maximally effective. 4. Pretreatment (1 h) of hippocampal cells with phorbol-12-myristate-13-acetate, a PKC activator, at increasing concentrations (1-100 ng x ml(-1)), resulted in a dose-dependent reduction in Abeta-induced toxicity, whereas the inactive 4alpha-phorbol had no effect. 5. Pretreatment (30 min) of hippocampal cells with GF 109203X (1 microm), a general PKC inhibitor, significantly attenuated the neuroprotective effect of resveratrol against Abeta-induced cell death. 6. Treatment of hippocampal cells with resveratrol (20 microm) also induced the phosphorylation of various isoforms of PKC leading to activation. 7. Taken together, the present results indicate that PKC is involved in the neuroprotective action of resveratrol against Abeta-induced toxicity.

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Available from: Wen Hua Zheng, Jul 16, 2015
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    • "Moreover, resveratrol slightly decreased the phosphorylation of PKC-d, but did not affect the phosphorylation of PKCí µí»¼/í µí»½II, PKC-í µí¼‡ (Ser916), and PKC-í µí¼ƒ (Thr538), suggesting that PKC-í µí»¿ (Thr505) was involved in the neuroprotective effects of resveratrol. In short, the PKC pathway played a major role in the neuroprotective-neurorescuing properties of resveratrol against Aí µí»½-induced toxicity in hippocampal neurons [43]. "
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    • "The activation of protein kinase C (PKC) may stimulate α-secretase and then non-amyloidogenic pathway in APP processing, resulting in a reduction in the production of Aβ [53]. Our group reported that dihydrochloride3-(1-[3-(dimethylamino) propyl]-1H-indol-3yl)-4- (1H-indol-3-yl)-1H-pyrrole-2,5-dione (GF 109203X), a PKC inhibitor, attenuated the neuroprotective effects of resveratrol against Aβinduced toxicity in hippocampal cell cultures [38]. Moreover, Western blot data suggested that resveratrol (20–30 μM) induced the phosphorylation of the PKC delta (δ) isoform, whose inhibition is required for initiation of the apoptotic pathway [54]. "
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