Yoshinori Mikami1, Toshiko Yamazawa2. 1. Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 1130033, Japan. 2. Department of Molecular Physiology, The Jikei University School of Medicine, 3-25-8 Nishi-Shimbashi, Minato-ku, Tokyo 1058461, Japan. Electronic address: toshiko1998@jikei.ac.jp.
Abstract
AIMS: The present study has been designed to explore the molecular mechanism of chlorogenic acid (CGA) in the protective effect against glutamate-induced neuronal cell death. MAIN METHODS: Cortical neurons in primary culture were exposed to 300 μM l-glutamic acid or vehicle, with or without 10 μM CGA or 10 μM MK-801. After 16 h, primary cultures were stained with propidium iodide (PI)/Hoechst or calcein. Double-staining with PI and Hoechst was performed to confirm whether cell death induced by glutamate was apoptotic. In addition, intracellular concentrations of Ca(2+) were observed using Ca(2+) indicator fura-2. KEY FINDINGS: We investigated the protective effects of CGA on glutamate-induced neuronal cell death using primary cultures of mouse cerebral cortex because the release of glutamate during brain ischemia triggers death of neurons. Glutamate-induced neuronal cell death was inhibited by treatment with CGA. In addition, CGA prevented the increase in intracellular concentrations of Ca(2+) caused by the addition of glutamate to cultured neurons. On the other hand, there was little effect of CGA on cell death induced by nitric oxide, which is downstream of the ischemic neuronal cell death. Our results suggested that the polyphenol CGA in coffee protects neurons from glutamate neurotoxicity by regulating Ca(2+) entry into neurons. SIGNIFICANCE: CGA in coffee may have clinical benefits for neurodegenerative diseases such as ischemic stroke.
AIMS: The present study has been designed to explore the molecular mechanism of chlorogenic acid (CGA) in the protective effect against glutamate-induced neuronal cell death. MAIN METHODS: Cortical neurons in primary culture were exposed to 300 μM l-glutamic acid or vehicle, with or without 10 μM CGA or 10 μM MK-801. After 16 h, primary cultures were stained with propidium iodide (PI)/Hoechst or calcein. Double-staining with PI and Hoechst was performed to confirm whether cell death induced by glutamate was apoptotic. In addition, intracellular concentrations of Ca(2+) were observed using Ca(2+) indicator fura-2. KEY FINDINGS: We investigated the protective effects of CGA on glutamate-induced neuronal cell death using primary cultures of mouse cerebral cortex because the release of glutamate during brain ischemia triggers death of neurons. Glutamate-induced neuronal cell death was inhibited by treatment with CGA. In addition, CGA prevented the increase in intracellular concentrations of Ca(2+) caused by the addition of glutamate to cultured neurons. On the other hand, there was little effect of CGA on cell death induced by nitric oxide, which is downstream of the ischemic neuronal cell death. Our results suggested that the polyphenol CGA in coffee protects neurons from glutamateneurotoxicity by regulating Ca(2+) entry into neurons. SIGNIFICANCE: CGA in coffee may have clinical benefits for neurodegenerative diseases such as ischemic stroke.
Authors: Olfa Rebai; Manel Belkhir; María Victoria Sanchez-Gomez; Carlos Matute; Sami Fattouch; Mohamed Amri Journal: Neurochem Res Date: 2017-09-25 Impact factor: 3.996
Authors: Nora E Gray; Armando Alcazar Magana; Parnian Lak; Kirsten M Wright; Joseph Quinn; Jan F Stevens; Claudia S Maier; Amala Soumyanath Journal: Phytochem Rev Date: 2017-09-20 Impact factor: 5.374
Authors: Mara Yone D Fernandes; Fernando Dobrachinski; Henrique B Silva; João Pedro Lopes; Francisco Q Gonçalves; Felix A A Soares; Lisiane O Porciúncula; Geanne M Andrade; Rodrigo A Cunha; Angelo R Tomé Journal: Sci Rep Date: 2021-05-18 Impact factor: 4.379