Gartanin Protects Neurons against Glutamate-Induced Cell Death in HT22 Cells: Independence of Nrf-2 but Involvement of HO-1 and AMPK

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

Research output: Journal article publicationJournal articleAcademic researchpeer-review

18 Citations (Scopus)

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.
Original languageEnglish
Pages (from-to)2267-2277
Number of pages11
JournalNeurochemical Research
Volume41
Issue number9
DOIs
Publication statusPublished - 1 Sep 2016

Keywords

  • AMP-activated protein kinase
  • Gartanin
  • Heme oxygenase 1
  • Neuroprotective
  • Nuclear factor erythroid-derived 2-like 2
  • Oxidative stress

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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