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KMID : 0811720050090000052
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Korean Journal of Physiology & Pharmacology
2005 Volume.9 No. 0 p.52 ~ p.0
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IL-6 Decreases Low Mg2+-induced Excitotoxicity in Cultured Rat Hippocampal Neurons by Inhibition of [Ca2+]i Spikes and Activation of RAS/MAPK and JAK-STAT
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Kim Sun-Mi
Kim Hee-Jung
Kim Tae-Hyeong
Shim Eun-Young
Ahn Seo-Hee
Lee Mun-Yong
Kim Seong-Yun
Rhie Duck-Joo
Jo Yang-Hyeok
Kim Myung-Suk
Hahn Sang-June
Yoon Shin-Hee
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Abstract
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IL-6 has been reported to have a potential role in neuronal survival, protection, differentiation, and neurodegeneration. We tested whether IL-6 can affect the neuronal cell death induced by exposure to 0.1 mM [Mg2+]o for 24 hr in 14 days cultured hippocampal neurons from embryonic day 17 rats. 0.1 mM [Mg2+]o evoked repetitive [Ca2+]i spikes and induced neuronal cell death. Treatment with IL-6 (10～100 ng/ml) protected neurons against low [Mg2+]o-induced neurotoxicity in dose-dependent manner. A brief treatment with IL-6 (50 ng/ml) for 10 min did not affect the [Ca2+]i spikes. The [Ca2+]i spikes significantly decreased following prolonged treatment with IL-6 (50 ng/ml) for 1 or 2 hr. The MAPK inhibitor U0126 (1μM) and the JAK-2 inhibitor AG490 (3μM) significantly suppressed the IL-6 (50 ng/ml)-induced cell survival, but the PI3K inhibitor LY294,002 (5μM) did not. The IL-6-induced decrease in the [Ca2+]i spikes was also inhibited by treatment with U0126 (1μM) and AG490 (3μM). In addition, treatment with IL-6 (50 ng/ml) for 15 min induced phosphorylation of STAT3 on Tyr705 and of MAPK on Thr202/Thr204, which dependent on JAK-2 in purified rat hippocampal neurons. These results suggest that IL-6 decreases 0.1 mM [Mg2+]o-induced neuronal cell death through inhibition of low [Mg2+]o-induced [Ca2+]i spikes and activation of RAS/MAPK and JAK-STAT in cultured rat hippocampal neurons (Supported by grant No. R01-2002-000-00334-0 from the Basic Research Program of the Korea Science & Engineering Foundation).
Source: Korean Journal of Physiology & Pharmacology.2005 Oct;9(Suppl I):S81-S81
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KEYWORD
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Ca2+ spikes, Hippocampal neuron, IL-6, Janus tyrosine kinase-2, Mitogen-activated protein kinase
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