NDLI: Resveratrol down-regulates a glutamate-induced tissue plasminogen activator <i>via</i> Erk and AMPK/mTOR pathways in rat primary cortical neurons

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Resveratrol down-regulates a glutamate-induced tissue plasminogen activator via Erk and AMPK/mTOR pathways in rat primary cortical neurons

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Food & Function Vol - 5 Issue - 4

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Resveratrol down-regulates a glutamate-induced tissue plasminogen activator via Erk and AMPK/mTOR pathways in rat primary cortical neurons

Content Provider	Royal Society of Chemistry (RSC)
Author	Kim, Yun Tae Kim, Young Bin Gonzales, Edson Luck T. Shin, Chan Young Lee, Eun Joo Cho, Kyu Suk Bahn, Geon Ho Lee, Jongmin Han, Seol-Heui Cheong, Jae Hoon Kwon, Kyoung Ja
Copyright Year	2014
Abstract	Resveratrol (3,5,4′-trihydroxy-trans-stilbene, RSV) is a polyphenolic compound present in a variety of plant species (including grapes) that produces a myriad of biological activities including anti-inflammatory, antioxidant and neuroprotective effects. In this study, we investigate the effects of resveratrol on the basal and glutamate-stimulated expression and activity of a tissue plasminogen activator (tPA) that plays neuromodulatory or neurotoxic roles in many different neurological situations. Under basal conditions, resveratrol decreased the tPA expression and activity without affecting the tPA mRNA level in rat primary cortical neurons. RSV induced AMPK phosphorylation and inhibited mTOR phosphorylation. Inhibition of AMPK phosphorylation using compound C prevented resveratrol-induced down-regulation of tPA activity. This suggested that AMPK/mTOR-dependent translational inhibition contributes to the down-regulation of the tPA. Under glutamate-stimulated conditions of rat primary cortical neurons, tPA activity and expression were increased along with increased tPA mRNA expression but afterward treatment of RSV inhibited the glutamate-induced increase in tPA activity and expression and tPA mRNA expression. Glutamate stimulation induced activation of Akt and MAPK pathways as well as mTOR which were inhibited by RSV. Interestingly, the Erk pathway inhibitor U0126, but neither PI3K-Akt inhibitor LY294002 nor p38 inhibitor SB203580, mimicked the inhibitory action of RSV on glutamate-induced tPA up-regulation. This suggested the essential role of Erk in the transcriptional up-regulation of tPA expression, which is targeted by RSV. Glutamate stimulation induced neuronal cell death as determined by PI staining and MTT assay. However, RSV protected the cultured rat primary cortical neurons from glutamate-induced cell death as paralleled with the changes in tPA expression. These results suggested that RSV can modulate tPA activity under basal and stimulated conditions by both translational and transcriptional mechanisms. The regulation of the tPA by RSV provides additional therapeutic targets on top of the growing number of molecular substrates of RSV's action in the brain.
Starting Page	951
Ending Page	960
Page Count	10
File Format	HTM / HTML PDF
ISSN	20426496
Volume Number	5
Issue Number	5
Journal	Food & Function
DOI	10.1039/c3fo60397k
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	AMPK MTT Erk Resveratrol Antioxidant Neuroprotection Tissue plasminogen activator Neurotoxicity Messenger RNA AMP-activated protein kinase Phosphorylation Mechanistic target of rapamycin Glutamic acid Protein kinase B Mitogen-activated protein kinase Enzyme inhibitor U0126 LY294002 P38 mitogen-activated protein kinases SB 203580 MTT assay
Content Type	Text
Resource Type	Article
Subject	Medicine Food Science

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