Involvement of Intracellular Ca(2+)-and PI3K-Dependent ERK Activation in TCDD-Induced Inhibition of Cell Proliferation in SK-N-SH Human Neuronal Cells
- Authors
- Yang, Seun-Ah; Lee, Yong-Soo; Jin, Da-Qing; Jung, Jae-Wook; Park, Byung-Chul; Lee, Yoon-Seok; Paek, Seung-Hwan; Jeong, Tae-Cheon; Choi, Han-Gon; Yong, Chul-Soon; Yoo, Bong-Kyu; Kim, Jung-Ae
- Issue Date
- Apr-2005
- Publisher
- 한국응용약물학회
- Keywords
- TCDD; neurotoxicity; intracellular Ca(2+); ERK; PI3K; proliferation; SK-N-SH human neuronal cells
- Citation
- 응용약물학회지(Biomolecules & Therapeutics), v.13, no.2, pp.78 - 83
- Indexed
- KCI
- Journal Title
- 응용약물학회지(Biomolecules & Therapeutics)
- Volume
- 13
- Number
- 2
- Start Page
- 78
- End Page
- 83
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/46027
- ISSN
- 1976-9148
- 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
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