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- Title
Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK.
- Authors
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
- Abstract
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.
- Subjects
NEURONS; GLUTAMIC acid; CELL death; NEURODEGENERATION; OXIDATIVE stress; PHARMACOLOGY
- Publication
Neurochemical Research, 2016, Vol 41, Issue 9, p2267
- ISSN
0364-3190
- Publication type
Article
- DOI
10.1007/s11064-016-1941-x