Abstract
Nonylphenol is an environmental endocrine disrupter. The effect of nonylphenol on intracellular free Ca2+ levels ([Ca2+]i) and viability in Madin-Darby canine kidney (MDCK) cells was explored. Nonylphenol increased [Ca2+]i in a concentration-dependent manner (EC50∼0.8 μM). Nonylphenol-induced Mn2+ entry demonstrated Ca2+ influx and removal of extracellular Ca2+ partly decreased the [Ca2+]i rise. The [Ca2+]i rise was inhibited by the protein kinase C activator, phorbol 13-myristate acetate (PMA) but not by L-type Ca2+ channel blockers. In Ca 2+-free medium, nonylphenol-induced [Ca2+]i rise was partly inhibited by pretreatment with 1 μM thapsigargin (an endoplasmic reticulum Ca2+ pump inhibitor). Conversely, nonylphenol pretreatment abolished thapsigargin-induced Ca2+ release. Nonylphenol-induced Ca2+ release was unaltered by inhibition of phospholipase C. At concentrations of 5-100 μM, nonylphenol killed cells in a concentration-dependent manner. The cytotoxic effect of 100 μM nonylphenol was not affected by preventing [Ca2+]i rises with BAPTA/AM. Collectively, this study shows that nonylphenol induced [Ca2+]i increase in MDCK cells via evoking Ca2+ entry through protein kinase C-regulated Ca2+ channels, and releasing Ca2+ from endoplasmic reticulum and other stores in a phospholipase C-independent manner. Nonylphenol also killed cells in a Ca2+-independent fashion.
Original language | English |
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Pages (from-to) | 370-377 |
Number of pages | 8 |
Journal | Drug Development Research |
Volume | 70 |
Issue number | 5 |
DOIs | |
State | Published - 08 2009 |
Externally published | Yes |
Keywords
- Ca
- Fura-2
- MDCK cells
- Nonylphenol