Title |
Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK
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Published in |
Neurochemical Research, May 2016
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DOI | 10.1007/s11064-016-1941-x |
Pubmed ID | |
Authors |
Xiao-yun Gao, Sheng-nan Wang, Xiao-hong Yang, Wen-jian Lan, Zi-wei Chen, Jing-kao Chen, Jian-hui Xie, Yi-fan Han, Rong-biao Pi, Xiao-bo Yang |
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. |
X Demographics
Geographical breakdown
Country | Count | As % |
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Australia | 1 | 100% |
Demographic breakdown
Type | Count | As % |
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Members of the public | 1 | 100% |
Mendeley readers
Geographical breakdown
Country | Count | As % |
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Unknown | 31 | 100% |
Demographic breakdown
Readers by professional status | Count | As % |
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Student > Ph. D. Student | 8 | 26% |
Student > Bachelor | 6 | 19% |
Student > Master | 3 | 10% |
Lecturer | 2 | 6% |
Unspecified | 2 | 6% |
Other | 6 | 19% |
Unknown | 4 | 13% |
Readers by discipline | Count | As % |
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Medicine and Dentistry | 6 | 19% |
Biochemistry, Genetics and Molecular Biology | 4 | 13% |
Pharmacology, Toxicology and Pharmaceutical Science | 3 | 10% |
Unspecified | 2 | 6% |
Nursing and Health Professions | 2 | 6% |
Other | 8 | 26% |
Unknown | 6 | 19% |