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Involvement of Intracellular Ca(2+)-and PI3K-Dependent ERK Activation in TCDD-Induced Inhibition of Cell Proliferation in SK-N-SH Human Neuronal Cells

Title
Involvement of Intracellular Ca(2+)-and PI3K-Dependent ERK Activation in TCDD-Induced Inhibition of Cell Proliferation in SK-N-SH Human Neuronal Cells
Author
최한곤
Keywords
TCDD; neurotoxicity; intracellular Ca(2+); ERK; PI3K; proliferation; SK-N-SH human neuronal cells
Issue Date
2005-04
Publisher
한국응용약물학회
Citation
Biomolecules & Therapeutics, v. 13, No. 2, Page. 78-83
Abstract
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) has previously shown to induce neurotoxicity through intracellular Ca2+ increase in rat neurons. In this study we investigated the role and signaling pathway of intracellular Ca2+ in TCDD-induced inhibition of neuronal cell proliferation in SK-N-SH human neuronal cells. We found that TCDD (10 nM) rapidly increased the level of intracellular Ca2+, which was completely blocked by the extracellular Ca2+ chelation with EGTA (1 mM) or by pretreatment of the cells with the non-selective cation channel blocker, flufenamic acid (200 M). However, pretreatment of the cells with dantrolene (25 M) and TMB-8 (10 M), intracellular Ca2+-release blockers, or a voltage-sensitive Ca2+ channel blocker, verapamil (100 M), failed to block the TCDD-induced Ca2+ increase in the cells. In addition, TCDD induced a rapid and transient activation of phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated kinase1/2 (ERK1/2), which was significantly blocked by the pretreatment with BAPTA, an intracellular Ca2+ chelator, and LY294002, a PI3K inhibitor. Furthermore, inhibitors of PI3K, ERK, or an intracellular Ca2+ chelator further potentiated the anti-proliferative effect of TCDD in the cells. Collectively, the results suggest that intracellular Ca2+ and PI3K-dependent activation of ERK1/2 may be involved in the TCDD-induced inhibition of cell proliferation in SK-N-SH human neuronal cells
URI
http://kiss.kstudy.com/thesis/thesis-view.asp?key=2524912http://repository.hanyang.ac.kr/handle/20.500.11754/110389
ISSN
1976-9148; 2005-4483
Appears in Collections:
COLLEGE OF PHARMACY[E](약학대학) > PHARMACY(약학과) > Articles
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