Nonylphenol-induced cytosolic Ca2+ elevation and death in renal tubular cells

Jeng Yu Tsai, Chorng Chih Huang, He Hsiung Cheng, Ko Long Lin, Wei Chuan Liao, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

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 languageEnglish
Pages (from-to)370-377
Number of pages8
JournalDrug Development Research
Volume70
Issue number5
DOIs
StatePublished - 08 2009
Externally publishedYes

Keywords

  • Ca
  • Fura-2
  • MDCK cells
  • Nonylphenol

Fingerprint

Dive into the research topics of 'Nonylphenol-induced cytosolic Ca2+ elevation and death in renal tubular cells'. Together they form a unique fingerprint.

Cite this