Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation

Cristina C. Teixeira, Kyle Mansfield, Caryn Hertkorn, Harry Ischiropoulos, Irving M. Shapiro

Research output: Contribution to journalArticle

Abstract

An elevation in inorganic phosphate (Pi) concentration activates epiphyseal chondrocyte apoptosis. To determine the mechanism of apoptosis, tibial chondrocytes were treated with Pi, and nitrate/nitrite (NO3-/NO2-) levels were determined. Pi induced a threefold increase in the NO3-/NO2- concentration; inhibitors of nitric oxide (NO) synthase activity and Pi transport significantly reduced NO3-/NO2- levels and prevented cell death. Furthermore, a dose-dependent increase in cell death was observed after exposure of chondrocytes to S-nitrosoglutathione. Pi increased caspase 3 activity 2.7-fold. Both caspase 1 and caspase 3 inhibitors protected chondrocytes from Pi-induced apoptosis. Pi caused a significant decrease in the mitochondrial membrane potential, while NO synthase inhibitors maintained mitochondrial function. While Pi caused thiol depletion, inhibition of Pi uptake or NO generation served to maintain glutathione levels. The results suggest that NO serves to mediate key metabolic events linked to Pi-dependent chondrocyte apoptosis.

Original languageEnglish (US)
Pages (from-to)C833-C839
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number3 50-3
DOIs
StatePublished - 2001

Keywords

  • Caspase
  • Epiphyseal chondrocyte
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Physiology
  • Cell Biology

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