頁籤選單縮合
題名 | The Antidepressant Mirtazapine-Induced Cytosolic Ca[fec7] Elevation and Cytotoxicity in Human Osteosarcoma Cells |
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作 者 | Pan, Chin-chuan; Cheng, He-hsiung; Huang, Chun-jen; Lu, Yih-chau; Chen, I-shu; Liu, Shiuh-inn; Hsu, Shu-shong; Chang, Hong-tai; Huang, Jong-khing; Chen, Jin-shyr; Jan, Chung-ren; | 書刊名 | 中國生理學雜誌 |
卷期 | 49:6 民95.12 |
頁次 | 頁290-297 |
分類號 | 418.214 |
關鍵詞 | Ca[fec7]; Fura-2; MG63 cells; Mirtazapine; Osteosarcoma cells; Thapsigargin; |
語文 | 英文(English) |
英文摘要 | The effect of the antidepressant mirtazapine on cytosolic free Ca²⁺ concentration ([Ca²⁺]]i) and viability has not been explored in any cell type. This study examined whether mirtazapine alters Ca²⁺ levels and causes cell death in osteoblast-like cells using MG63 human osteosarcoma cells as a model. [Ca²⁺]]i and cell viability were measured using the fluorescent dyes fura-2 and WST-1, respectively. Mirtazapine at concentrations above 250 μM increased [Ca²⁺]]i in a concentration-dependent manner. The Ca²⁺ signal was reduced by 60% by removing extracellular Ca²⁺. The mirtazapine-induced Ca²⁺ influx was sensitive to blockade of nifedipine and verapamil. In Ca²⁺-free medium, after pretreatment with 1.5 mM mirtazapine, 1 μM thapsigargin (an endoplasmic reticulum Ca²⁺ pump inhibitor), 2 μM CCCP (a mitochondrial uncoupler), and 1 μM ionomycin failed to release more stored Ca²⁺; conversely, pretreatment with thapsigargin, CCCP and ionomycin abolished mirtazapine-induced Ca²⁺ release. Inhibition of phospholipase C with 2 μM U73122 did not change mirtazapine-induced [Ca²⁺]]i increase. Seal of Ca²⁺ movement across the plasma membrane with 50 μM extracellular La(superscript 3+) enhanced 1 μM thapsigargin-induced [Ca²⁺]]i increase, suggesting that Ca²⁺ efflux played a role in lowering thapsigargin-induced [Ca²⁺]]i increase; however, the same La(superscript 3+) treatment did not alter mirtazapine-induced [Ca²⁺]]i increase. At concentrations of 500 μM and 1000 μM, mirtazapine killed 30% and 60% cells, respectively. The cytotoxicity was not reversed by chelating cytosolic Ca²⁺ with BAPTA. Collectively, in MG63 cells, mirtazapine induced a [Ca²⁺]]i increase by causing Ca²⁺ release from stores and Ca²⁺ influx from extracellular space. Furthermore, mirtazapine caused cytotoxicity at higher concentrations in a Ca²⁺-dissociated manner. |
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