Grape seed extract acting on astrocytes reveals neuronal protection against oxidative stress via interleukin-6-mediated mechanisms.
Grape polyphenols are known to protect neurons against oxidative stress. We used grape seed extract (GSE) from "Koshu" grapes (Vitis vinifera) containing a variety of polyphenols, and performed transcriptome analysis to determine the effects of GSE on primary cultures of astrocytes in the hippocampus. GSE upregulated various mRNAs for cytokines, among which interleukin-6 (IL-6) showed the biggest increase after treatment with GSE. The GSE-evoked increase in IL-6 mRNAs was confirmed by quantitative RT-PCR. We also detected IL-6 proteins by ELISA in the supernatant of GSE-treated astrocytes. We made an oxidative stress-induced neuronal cell death model in vitro using a neuron rich culture of the hippocampus. Treatment of the neurons with H(2)O(2) caused neuronal cell death in a time- and concentration-dependent manner. Exogenously applied IL-6 protected against the H(2)O(2)-induced neuronal cell death, which was mimicked by endogenous IL-6 produced by GSE-treated astrocytes. Taken together, GSE acting on astrocytes increased IL-6 production, which functions as a neuroprotective paracrine, could protect neuronal cells from death by oxidative stress.
Fujishita
Kayoko
K
Department of Pharmacology, Interdisciplinary Graduate School of Medicine and Engineering, University of Yamanashi, Yamanashi, 409-3898, Japan.
Ozawa
Tetsuro
T
Shibata
Keisuke
K
Tanabe
Shihori
S
Sato
Yoji
Y
Hisamoto
Masashi
M
Okuda
Tohru
T
Koizumi
Schuichi
S
D000818:Animals; D001253:Astrocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D019610:Cytoprotection / Q000187:drug effects*; D020869:Gene Expression Profiling; D056604:Grape Seed Extract / Q000494:pharmacology*; D006861:Hydrogen Peroxide / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics* / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology; D018384:Oxidative Stress / Q000187:drug effects*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism; D013997:Time Factors; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics
D056604:Grape Seed Extract; D015850:Interleukin-6; D018696:Neuroprotective Agents; D012333:RNA, Messenger; D006861:Hydrogen Peroxide