Neuroprotective effects of resveratrol and epigallocatechin gallate polyphenols are mediated by the activation of protein kinase C gamma

Abstract

Polyphenols such as epigallocatechin gallate (EGCG) and resveratrol have received a great deal of attention because they may contribute to the purported neuroprotective action of the regular consumption of green tea and red wine. Many studies, including those published by our group, suggest that this protective action includes their abilities to prevent the neurotoxic effects of beta-amyloid, a protein whose accumulation likely plays a pivotal role in Alzheimer's disease. Moreover, the scavenging activities of polyphenols on reactive oxygen species and their inhibitory action of cyclooxygenase likely explain, at least in part, their antioxidant and anti-inflammatory activities. Besides these well-documented properties, the modulatory action of these polyphenols on intracellular signaling pathways related to cell death/survival (e.g., protein kinase C, PKC) has yet to be investigated in detail. Using rat hippocampal neuronal cells, we aimed to investigate here the effects of EGCG and resveratrol on cell death induced by GF 109203X, a selective inhibitor of PKC. The MTT/resazurin and spectrin assays indicated that EGCG and resveratrol protected against GF 109203X-induced cell death and cytoskeleton degeneration, with a maximal effect at 1 and 3 μM, respectively. Moreover, immunofluorescence data revealed that cells treated with these polyphenols increased PKC gamma (γ) activation and promoted neuronal interconnections. Finally, we found that the protective effects of both polyphenols on the cytoskeleton and synaptic plasticity were mediated by the PKCγ subunit. Taken together, the results suggest that PKC, and more specifically its γ subunit, plays a critical role in the protective action of EGCG and resveratrol on neuronal integrity.

Wine consumption, cognitive function and dementias – A relationship?

“…PKC modulates cell viability which protects certain neuronal cells against A␤-induced toxicity. Resveratrol and other phenolic compounds such as epigallocatechin gallate have been observed to protect hippocampal cells against A␤-induced toxicity by activating PKC [113,123,124], and specific binding sites for resveratrol have been identified in the rat brain [114], as have receptors for the green tea catechin gallates.…”

Protective Effects of Resveratrol in a Rat Model of Ischemia-Reperfusion Injury of Sciatic Nerve

“…There was not a statistically significant difference for serum MDA (Figure 4) and tissue TAS ( Figure 5) levels according to the groups (p=0.278 and p=0.069, respectively). 14-1,43) 10,81±4,32 (6,92) 2…”

“…Resveratrol is a polyphenol compound found especially in red wine, red grapes, blackberries, sour cherries and peanuts (6). It has antioxidant, antiinflammatory, cardioprotective, antidiabetic, anticancer, and neuroprotective properties, which are also effective in protecting liver and kidneys (7)(8)(9)(10).…”

Signaling Pathways Relevant to Cognition-Enhancing Drug Targets

“…This kinase was linked to the individual differences observed in the cognitive status of aging rats (Coalombo et al 1997;Colombo and Gallagher 2002;Menard and Quirion 2012b), and its activation in small groups of hippocampal or cortical neurons improves old rat performances in the MWM task (Zhang et al 2009). PKCγ activity may promote neuronal interconnections (Menard et al 2013a) and synaptogenesis (Hongpaisan and Alkon 2007) and protects against neurodegeneration (for a review, see Sun and Alkon 2010). PKC enzymes can be activated by Ca 2+ , DAG, arachidonic acid, phospholipids, and phorbol esters.…”