Glutathione depletion promotes aluminum-mediated cell death of PC12 cells.
Exposure of rat phenochromocytoma cells (PC12 cells) to aluminum maltolate complex, Al(maltol)3, induced a decrease in intracellular glutathione (GSH) concentration, resulting in a facilitated release of lactate dehydrogenase (LDH) from the cell and an increase in trypan blue-stained cells. Similar phenomena were observed as the cells were treated with L-buthione-[S,R]-sulfoximine (BSO) in the presence of Al(maltol)3. On the other hand, treatment of PC 12 cells with BSO alone in the absence of Al(maltol)3 did not affect the cell viability. Pre-treatment of PC12 cells with N-acetylcysteine (NAC) for 30 min before a 48 h-exposure to Al(maltol)3 effectively protected the cells from Al(maltol)3 toxicity by increasing intracellular GSH concentration. NAC also effectively inhibited reactive oxygen species (ROS) generation induced by treatment of the cells with Al(maltol)3. However, several lipophilic radical scavengers such as alpha-tocopherol and 3(2)-tert-butyl-4-hydroxyanisole, and an iron chelator, desferrioxamine, did not prevent Al(maltol)3-mediated ROS production or the decrease of cell viability. Based on these results, we discussed the role of intracellular GSH against the onset of aluminum toxicity in the context of ROS production.
Satoh
Eiko
E
Department of Clinical Chemistry, Faculty of Pharmaceutical Sciences, Hokuriku University, Ishikawa, Japan.
Okada
Morihiro
M
Takadera
Tsuneo
T
Ohyashiki
Takao
T
D000818:Animals; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005978:Glutathione / Q000172:deficiency*; D007424:Intracellular Fluid / Q000187:drug effects / Q000378:metabolism; D009942:Organometallic Compounds / Q000633:toxicity*; D016716:PC12 Cells; D011753:Pyrones / Q000633:toxicity*; D051381:Rats; D017382:Reactive Oxygen Species / Q000378:metabolism
D009942:Organometallic Compounds; D011753:Pyrones; D017382:Reactive Oxygen Species; C067527:aluminum maltolate; D005978:Glutathione