Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
9037049 | Toxicology Letters | 2005 | 8 Pages |
Abstract
The effect of the environmental toxicant nonylphenol on cytosolic free Ca2+ concentration ([Ca2+]i) and proliferation has not been explored in human osteoblast-like cells. This study examined whether nonylphenol alters Ca2+ levels and causes cell death in MG63 human osteosarcoma cells. [Ca2+]i and cell death were measured using the fluorescent dyes fura-2 and WST-1 respectively. Nonylphenol at concentrations above 3 μM increased [Ca2+]i in a concentration-dependent manner. The Ca2+ signal was reduced by 90% by removing extracellular Ca2+. The nonylphenol-induced Ca2+ influx was insensitive to blockade of L-type Ca2+ channel blockers. After pretreatment with 10 μM nonylphenol, 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor) failed to induce [Ca2+]i rises. Inhibition of phospholipase C with 2 μM U73122 did not change nonylphenol-induced [Ca2+]i rises. The nonylphenol-induced [Ca2+]i rises were enhanced or inhibited by phorbol myristate acetate or GF 109203X, respectively. At concentrations of 10 and 20 μM nonylphenol killed 55% and 100% cells, respectively. The cytotoxic effect of 10 μM nonylphenol was unaltered by pre-chelating cytosolic Ca2+ with BAPTA. Collectively, in MG63 cells, nonylphenol induced [Ca2+]i rises by causing Ca2+ release from intracellular stores and Ca2+ influx from extracellular space. Furthermore, nonylphenol can cause Ca2+-unrelated cytotoxicity in a concentration-dependent manner.
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Authors
Jue-Long Wang, Chung-Shin Liu, Ko-Long Lin, Chiang-Ting Chou, Ching-Hong Hsieh, Chih-Hung Chang, Wei-Chuan Chen, Shiuh-Inn Liu, Shu-Shong Hsu, Hong-Tai Chang, Chung-Ren Jan,