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: Motoharu Sakaue, Naoko Mori, Maiko Okazaki, Erika Kadowaki, Takuya Kaneko, Natsuko Hemmi, Hitomi Sekiguchi, Takehiro Maki, Aisa Ozawa, Shuntaro Hara, Kazuyoshi Arishima, Masako Yamamoto
• Journal: Journal of neuroscience research (J Neurosci Res) Vol. 89 Issue 7 Pg. 1052-8 (Jul 2011) ISSN: 1097-4547 [Electronic] United States
• PMID: 21488088 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2011 Wiley-Liss, Inc.

Chemical References

• Methylmercury Compounds
• Neuroprotective Agents
• Vitamin K

Topics

• Animals
• Animals, Newborn
• Cell Death (drug effects, physiology)
• Cell Line, Tumor
• Disease Models, Animal
• Humans
• In Vitro Techniques
• Mercury Poisoning, Nervous System (metabolism, pathology, prevention & control)
• Methylmercury Compounds (antagonists & inhibitors, toxicity)
• Nerve Degeneration (chemically induced, drug therapy, pathology)
• Neurons (drug effects, metabolism, pathology)
• Neuroprotective Agents (pharmacology, therapeutic use)
• Rats
• Rats, Wistar
• Vitamin K (analogs & derivatives, pharmacology, therapeutic use)