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Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK.
Gao, Xiao-Yun; Wang, Sheng-Nan; Yang, Xiao-Hong; Lan, Wen-Jian; Chen, Zi-Wei; Chen, Jing-Kao; Xie, Jian-Hui; Han, Yi-Fan; Pi, Rong-Biao; Yang, Xiao-Bo.
Afiliação
  • Gao XY; Department of Anesthesiology, Guangdong Provincial Hospital of Traditional Chinese Medicine, Guangzhou, 510120, China.
  • Wang SN; Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
  • Yang XH; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.
  • Lan WJ; Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
  • Chen ZW; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.
  • Chen JK; Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
  • Xie JH; Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
  • Han YF; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.
  • Pi RB; Department of Pharmacology and Toxicology, School of Pharmaceutical Sciences, Sun Yat-Sen University, Guangzhou, 510006, China.
  • Yang XB; International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of Guangdong, Guangzhou, 510006, China.
Neurochem Res ; 41(9): 2267-77, 2016 Sep.
Article em En | MEDLINE | ID: mdl-27161377
Oxidative stress mediates the pathogenesis of neurodegenerative disorders. Gartanin, a natural xanthone of mangosteen, possesses multipharmacological activities. Herein, the neuroprotection capacity of gartanin against glutamate-induced damage in HT22 cells and its possible mechanism(s) were investigated for the first time. Glutamate resulted in cell death in a dose-dependent manner and supplementation of 1-10 µM gartanin prevented the detrimental effects of glutamate on cell survival. Additional investigations on the underlying mechanisms suggested that gartanin could effectively reduce glutamate-induced intracellular ROS generation and mitochondrial depolarization. We further found that gartanin induced HO-1 expression independent of nuclear factor erythroid-derived 2-like 2 (Nrf2). Subsequent studies revealed that the inhibitory effects of gartanin on glutamate-induced apoptosis were partially blocked by small interfering RNA-mediated knockdown of HO-1. Finally, the protein expression of phosphorylation of AMP-activated protein kinase (AMPK) and its downstream signal molecules, Sirtuin activator (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), increased after gartanin treatment. Taken together, these findings suggest gartanin is a potential neuroprotective agent against glutamate-induced oxidative injury partially through increasing Nrf-2-independed HO-1 and AMPK/SIRT1/PGC-1α signaling pathways.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apoptose / Xantonas / Heme Oxigenase-1 / Fator 2 Relacionado a NF-E2 / Proteínas Quinases Ativadas por AMP / Proteínas de Membrana / Neurônios Idioma: En Revista: Neurochem Res Ano de publicação: 2016 Tipo de documento: Article País de afiliação: China

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Apoptose / Xantonas / Heme Oxigenase-1 / Fator 2 Relacionado a NF-E2 / Proteínas Quinases Ativadas por AMP / Proteínas de Membrana / Neurônios Idioma: En Revista: Neurochem Res Ano de publicação: 2016 Tipo de documento: Article País de afiliação: China