title: Vitamin K has the potential to protect neurons from methylmercury-induced cell death in vitro.
abstract: Vitamin K (VK) has a protective effect on neural cells. Methylmercury is a neurotoxicant that directly induces neuronal death in vivo and in vitro. Therefore, in the present study, we hypothesized that VK inhibits the neurotoxicity of methylmercury. To prove our hypothesis in vitro, we investigated the protective effects of VKs (phylloquinone, vitamin K(1); menaquinone-4, vitamin K(2) ) on methylmercury-induced death in primary cultured neurons from the cerebella of rat pups. As expected, VKs inhibited the death of the primary cultured neurons. It has been reported that the mechanisms underlying methylmercury toxicity involve a decrement of intracellular glutathione (GSH). Actually, treatment with GSH and a GSH inducer, N-acetyl cysteine, inhibited methylmercury-induced neuronal death in the present study. Thus, we investigated whether VKs also have protective effects against GSH-depletion-induced cell death by employing two GSH reducers, L-buthionine sulfoximine (BSO) and diethyl maleate (DEM), in primary cultured neurons and human neuroblastoma IMR-32 cells. Treatment with VKs affected BSO- and DEM-induced cell death in both cultures. On the other hand, the intracellular GSH assay showed that VK(2), menaquinone-4, did not restore the reduced GSH amount induced by methylmercury or BSO treatments. These results indicate that VKs have the potential to protect neurons against the cytotoxicity of methylmercury and agents that deplete GSH, without increasing intracellular GSH levels. The protective effect of VKs may lead to the development of treatments for neural diseases involving GSH depletion.
authors.affiliation: Department of Anatomy II, School of Veterinary Medicine, Azabu University, Sagamihara, Japan. sakaue@azabu-u.ac.jp
authors.forename: Motoharu
authors.initials: M
authors.lastname: Sakaue
authors.forename: Naoko
authors.initials: N
authors.lastname: Mori
authors.forename: Maiko
authors.initials: M
authors.lastname: Okazaki
authors.forename: Erika
authors.initials: E
authors.lastname: Kadowaki
authors.forename: Takuya
authors.initials: T
authors.lastname: Kaneko
authors.forename: Natsuko
authors.initials: N
authors.lastname: Hemmi
authors.forename: Hitomi
authors.initials: H
authors.lastname: Sekiguchi
authors.forename: Takehiro
authors.initials: T
authors.lastname: Maki
authors.forename: Aisa
authors.initials: A
authors.lastname: Ozawa
authors.forename: Shuntaro
authors.initials: S
authors.lastname: Hara
authors.forename: Kazuyoshi
authors.initials: K
authors.lastname: Arishima
authors.forename: Masako
authors.initials: M
authors.lastname: Yamamoto
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D016923:Cell Death / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D006801:Humans; D066298:In Vitro Techniques; D020262:Mercury Poisoning, Nervous System / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008767:Methylmercury Compounds / Q000037:antagonists & inhibitors* / Q000633:toxicity; D009410:Nerve Degeneration / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D018696:Neuroprotective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar; D014812:Vitamin K / Q000031:analogs & derivatives / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D008767:Methylmercury Compounds; D018696:Neuroprotective Agents; D014812:Vitamin K