Characterization of antioxidant protection of cultured neural progenitor cells (NPC) against methylmercury (MeHg) toxicity.
Methylmercury (MeHg) is an environmental pollutant known to cause neurobehavioral defects and is especially toxic to the developing brain. With recent studies showing that fetal exposure to low-dose MeHg causes developmental abnormalities, it is therefore important to find ways to combat its effects as well as to clarify the mechanism(s) underlying MeHg toxicity. In the present study, the effects of MeHg on cultured neural progenitor cells (NPC) derived from mouse embryonic brain were investigated. We first confirmed the vulnerability of embryonic NPC to MeHg toxicity, NPC from the telencephalon were more sensitive to MeHg compared to those from the diencephalon. Buthionine sulfoximine (BSO) which is known to inhibit glutathione synthesis accelerated MeHg toxicity. Furthermore, antioxidants such as N-acetyl cysteine and alpha-tocopherol dramatically rescued the NPC from MeHg's toxic effects. Interestingly, a 12 hr delay in the addition of either antioxidant was still able to prevent the cells from undergoing cell death. Although it is now difficult to avoid MeHg exposure from our environment and contaminated foods, taking anti-oxidants from foods or supplements may prevent or diminish the toxicological effects of MeHg.
Watanabe
Jun
J
Department of Anatomy, School of Medicine, Showa University.
Nakamachi
Tomoya
T
Ogawa
Tetsuo
T
Naganuma
Akira
A
Nakamura
Masahisa
M
Shioda
Seiji
S
Nakajo
Sigeo
S
D000818:Animals; D000975:Antioxidants / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019328:Buthionine Sulfoximine / Q000494:pharmacology; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004027:Diencephalon / Q000187:drug effects / Q000196:embryology / Q000473:pathology; D004347:Drug Interactions; D004785:Environmental Pollutants / Q000633:toxicity*; D005978:Glutathione / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D008767:Methylmercury Compounds / Q000633:toxicity*; D051379:Mice; D008813:Mice, Inbred ICR; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013687:Telencephalon / Q000187:drug effects / Q000196:embryology / Q000473:pathology
D000975:Antioxidants; D004785:Environmental Pollutants; D008767:Methylmercury Compounds; D019328:Buthionine Sulfoximine; D005978:Glutathione