Methylmercury causes oxidative stress and cytotoxicity in microglia: attenuation by 15-deoxy-delta 12, 14-prostaglandin J2.
Methylmercury (MeHg) causes severe neurological disorders in the central nervous system. This study focused on the effects of MeHg on microglia, macrophage-like cells that reside in the CNS important in neuro-immune interactions. The murine N9 microglial cell line was used in this set of study. MeHg caused reactive oxygen species generation, mitochondrial depolarization and aconitase inactivation, all of which were signs of cellular oxidative stress. MeHg greatly increased microglial IL-6 secretion despite the fact that it severely inhibited protein synthesis. The concentration that caused 50% cell death in 24 h was approximately 9 microM. Pretreatment of microglia with the prostaglandin derivative, 15-deoxy-delta 12, 14-Prostaglandin J2 attenuated MeHg induced cell death. The saving effect did not appear to be mediated through activation of peroxisome proliferator activated receptors (PPAR) since other agonists of these receptors did not prevent MeHg induced microglial death.
Garg
Tarun K
TK
Department of Neurobiology and Developmental Sciences, University of Arkansas for Medical Sciences, 4301 W. Markham St., Little Rock, AR 72205, USA.
Chang
Jason Y
JY
D000154:Aconitate Hydratase / Q000378:metabolism; D000704:Analysis of Variance; D000818:Animals; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003601:Cytotoxicity Tests, Immunologic / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006861:Hydrogen Peroxide / Q000494:pharmacology; D007155:Immunologic Factors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D017628:Microglia / Q000187:drug effects*; D008928:Mitochondria / Q000187:drug effects; D008954:Models, Biological; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D015230:Prostaglandin D2 / Q000031:analogs & derivatives* / Q000494:pharmacology; D017382:Reactive Oxygen Species / Q000378:metabolism; D013997:Time Factors
C097240:15-deoxy-delta(12,14)-prostaglandin J2; D007155:Immunologic Factors; D015850:Interleukin-6; D008767:Methylmercury Compounds; D017382:Reactive Oxygen Species; D006861:Hydrogen Peroxide; D000154:Aconitate Hydratase; D015230:Prostaglandin D2