Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation

Cristina 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)
JournalAmerican Journal of Physiology - Cell Physiology
Volume281
Issue number3 50-3
StatePublished - 2001

Fingerprint

Chondrocytes
Nitric Oxide
Phosphates
Apoptosis
Cell death
Nitric Oxide Synthase
Caspase 3
S-Nitrosoglutathione
Cell Death
Caspase 1
Nitrites
Sulfhydryl Compounds
Caspase Inhibitors
Nitrates
Mitochondrial Membrane Potential
Glutathione
Membranes

Keywords

  • Caspase
  • Epiphyseal chondrocyte
  • Nitric oxide synthase

ASJC Scopus subject areas

  • Clinical Biochemistry
  • Cell Biology
  • Physiology
  • Physiology (medical)

Cite this

Teixeira, C., Mansfield, K., Hertkorn, C., Ischiropoulos, H., & Shapiro, I. M. (2001). Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation. American Journal of Physiology - Cell Physiology, 281(3 50-3).

Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation. / Teixeira, Cristina; Mansfield, Kyle; Hertkorn, Caryn; Ischiropoulos, Harry; Shapiro, Irving M.

In: American Journal of Physiology - Cell Physiology, Vol. 281, No. 3 50-3, 2001.

Research output: Contribution to journalArticle

Teixeira, C, Mansfield, K, Hertkorn, C, Ischiropoulos, H & Shapiro, IM 2001, 'Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation', American Journal of Physiology - Cell Physiology, vol. 281, no. 3 50-3.
Teixeira, Cristina ; Mansfield, Kyle ; Hertkorn, Caryn ; Ischiropoulos, Harry ; Shapiro, Irving M. / Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation. In: American Journal of Physiology - Cell Physiology. 2001 ; Vol. 281, No. 3 50-3.
@article{47163eef4bfe4aad88b3155558d4a88f,
title = "Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation",
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.",
keywords = "Caspase, Epiphyseal chondrocyte, Nitric oxide synthase",
author = "Cristina Teixeira and Kyle Mansfield and Caryn Hertkorn and Harry Ischiropoulos and Shapiro, {Irving M.}",
year = "2001",
language = "English (US)",
volume = "281",
journal = "American Journal of Physiology - Cell Physiology",
issn = "0363-6143",
publisher = "American Physiological Society",
number = "3 50-3",

}

TY - JOUR

T1 - Phosphate-induced chondrocyte apoptosis is linked to nitric oxide generation

AU - Teixeira, Cristina

AU - Mansfield, Kyle

AU - Hertkorn, Caryn

AU - Ischiropoulos, Harry

AU - Shapiro, Irving M.

PY - 2001

Y1 - 2001

N2 - 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.

AB - 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.

KW - Caspase

KW - Epiphyseal chondrocyte

KW - Nitric oxide synthase

UR - http://www.scopus.com/inward/record.url?scp=0034822944&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0034822944&partnerID=8YFLogxK

M3 - Article

VL - 281

JO - American Journal of Physiology - Cell Physiology

JF - American Journal of Physiology - Cell Physiology

SN - 0363-6143

IS - 3 50-3

ER -