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Neurochemical Research

, Volume 41, Issue 9, pp 2267–2277 | Cite as

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
Original Paper

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.

Keywords

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

Abbreviations

PD

Parkinson’s disease

AD

Alzheimer’s disease

ROS

Reactive oxygen species

ΔΨm

Mitochondrial membrane potential

HO-1

Heme oxygenase 1

Nrf-2

Nuclear factor erythroid-derived 2-like 2

AMPK

AMP-activated protein kinase

H2DCF-DA

H2DCF-DA dichlorodihydrofluorescein diacetate

DHE

Dihydroethidium

R123

Rhodamine 123

siRNA

Small interfering RNA

LC3

Microtubule-associated protein light chain 3

PPARα

Peroxisome proliferator-activated receptor α

SIRT1

Sirtuin activator 1

PGC-1α

Peroxisome proliferator-activated receptor-γ coactivator-1α

Notes

Acknowledgments

This study was supported by Guangdong Provincial International Cooperation Project of Science & Technology (No. 2013B051000038), National Natural Science Foundation of China (No. 31371070) and the Fundamental Research Funds for the Central Universities (No. 15ykjc08b) to R. Pi.

Compliance with Ethical Standards

Conflict of interest

All other authors declare no conflict of interest.

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Xiao-yun Gao
    • 1
  • Sheng-nan Wang
    • 2
    • 3
  • Xiao-hong Yang
    • 2
    • 3
  • Wen-jian Lan
    • 2
  • Zi-wei Chen
    • 2
    • 3
  • Jing-kao Chen
    • 2
    • 3
  • Jian-hui Xie
    • 4
  • Yi-fan Han
    • 3
    • 5
  • Rong-biao Pi
    • 2
    • 3
    • 6
  • Xiao-bo Yang
    • 4
  1. 1.Department of AnesthesiologyGuangdong Provincial Hospital of Traditional Chinese MedicineGuangzhouChina
  2. 2.Department of Pharmacology and Toxicology, School of Pharmaceutical SciencesSun Yat-Sen UniversityGuangzhouChina
  3. 3.International Joint Laboratory (SYSU-PolyU HK) of Novel Anti-Dementia Drugs of GuangdongGuangzhouChina
  4. 4.Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine SyndromeThe Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhouChina
  5. 5.Department of Applied Biology and Chemical Technology, Institute of Modern Chinese MedicineThe Hong Kong Polytechnic UniversityHung Hom, Hong KongChina
  6. 6.Guangdong Province Key Laboratory of Brain Function and Disease, Zhongshan School of MedicineSun Yat-sen UniversityGuangzhouChina

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