Hydrogen sulfide protects astrocytes against H(2)O(2)-induced neural injury via enhancing glutamate uptake.
Excess extracellular glutamate, the main excitatory neurotransmitter, may result in excitotoxicity and neural injury. The present study was designed to study the effect of hydrogen sulfide (H(2)S), a novel neuromodulator, on hydrogen peroxide (H(2)O(2)) -induced glutamate uptake impairment and cellular injuries in primary cultured rat cortical astrocytes. We found that NaHS (an H(2)S donor, 0.1-1000 microM) reversed H(2)O(2)-induced cellular injury in a concentration-dependent manner. This effect was attenuated by L-trans-pyrrolidine-2,4-dicarboxylic (PDC), a specific glutamate uptake inhibitor. Moreover, NaHS significantly increased [(3)H]glutamate transport in astrocytes treated with H(2)O(2), suggesting that H(2)S may protect astrocytes via enhancing glutamate uptake function. NaHS also reversed H(2)O(2)-impaired glutathione (GSH) production. Blockade of glutamate uptake with PDC attenuated this effect, indicating that the effect of H(2)S on GSH production is secondary to the stimulation of glutamate uptake. In addition, it was also found that H(2)S may promote glutamate uptake activity via decreasing ROS generation, enhancing ATP production and suppressing ERK1/2 activation. In conclusion, our findings provide direct evidence that H(2)S has potential therapeutic value for oxidative stress-induced brain damage via a mechanism involving enhancing glutamate uptake function.
Lu
Ming
M
Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Hu
Li-Fang
LF
Hu
Gang
G
Bian
Jin-Song
JS
D000255:Adenosine Triphosphate / Q000378:metabolism; D000393:Air Pollutants / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015153:Blotting, Western; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism*; D005978:Glutathione / Q000378:metabolism; D006861:Hydrogen Peroxide / Q000494:pharmacology*; D006862:Hydrogen Sulfide / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D016877:Oxidants / Q000494:pharmacology*; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D013347:Subcellular Fractions
D000393:Air Pollutants; D016877:Oxidants; D017382:Reactive Oxygen Species; D018698:Glutamic Acid; D000255:Adenosine Triphosphate; D006861:Hydrogen Peroxide; D005978:Glutathione; D006862:Hydrogen Sulfide