Nitrosative stress induces osteoblast apoptosis through downregulating MAPK-mediated NFκB/AP-1 activation and subsequent Bcl-XL expression

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Abstract

During inflammation, a large amount of reactive oxygen species is produced and causes insults to osteoblasts. This study was aimed to evaluate the molecular mechanisms of sodium nitroprusside (SNP)-induced insults to rat osteoblasts. Exposure of osteoblasts, prepared from neonatal rat calvaria to SNP increased the levels of cellular nitric oxide and intracellular reactive oxygen species, and simultaneously induced apoptotic insults in concentration- or time-dependent manners. Exposure of rat osteoblasts to SNP time-dependently decreased antiapoptotic Bcl-XL messenger RNA and protein syntheses. Treatment of rat osteoblasts with SNP decreased the translocation of transcription factors nuclear factor-kappaB (NFκB) and activator protein (AP)-1 from the cytoplasm to nuclei. Sequentially, phosphorylations of the mitogen-activated protein kinases (MAPKs) of ERK1/2, JNK1/2, and p38 MAPK decreased following SNP administration. Application of ERK1 and JNK1 small interference (si)RNAs into rat osteoblasts decreased the translation of these MAPKs and synergistically enlarged SNP-caused alterations in Bcl-XL mRNA expression and cell apoptosis. Therefore, this study shows that the SNP-induced nitrosative stress decreased Bcl-XL expression, and then induced apoptotic insults to rat osteoblasts through downregulating phosphorylation of MAPKs and subsequent activation of NFκB and AP-1.

Original languageEnglish
Pages (from-to)359-365
Number of pages7
JournalChemico-Biological Interactions
Volume184
Issue number3
DOIs
Publication statusPublished - Mar 2010

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Osteoblasts
Transcription Factor AP-1
Nitroprusside
Mitogen-Activated Protein Kinases
Down-Regulation
Chemical activation
Rats
Apoptosis
Phosphorylation
Reactive Oxygen Species
Messenger RNA
Mitogen-Activated Protein Kinase 1
p38 Mitogen-Activated Protein Kinases
RNA Interference
Skull
Nitric Oxide
Cytoplasm
Transcription Factors
RNA
Inflammation

Keywords

  • Bcl-X
  • MAPKs
  • NFκB/AP-1
  • Nitrosative stress
  • Osteoblasts

ASJC Scopus subject areas

  • Toxicology

Cite this

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title = "Nitrosative stress induces osteoblast apoptosis through downregulating MAPK-mediated NFκB/AP-1 activation and subsequent Bcl-XL expression",
abstract = "During inflammation, a large amount of reactive oxygen species is produced and causes insults to osteoblasts. This study was aimed to evaluate the molecular mechanisms of sodium nitroprusside (SNP)-induced insults to rat osteoblasts. Exposure of osteoblasts, prepared from neonatal rat calvaria to SNP increased the levels of cellular nitric oxide and intracellular reactive oxygen species, and simultaneously induced apoptotic insults in concentration- or time-dependent manners. Exposure of rat osteoblasts to SNP time-dependently decreased antiapoptotic Bcl-XL messenger RNA and protein syntheses. Treatment of rat osteoblasts with SNP decreased the translocation of transcription factors nuclear factor-kappaB (NFκB) and activator protein (AP)-1 from the cytoplasm to nuclei. Sequentially, phosphorylations of the mitogen-activated protein kinases (MAPKs) of ERK1/2, JNK1/2, and p38 MAPK decreased following SNP administration. Application of ERK1 and JNK1 small interference (si)RNAs into rat osteoblasts decreased the translation of these MAPKs and synergistically enlarged SNP-caused alterations in Bcl-XL mRNA expression and cell apoptosis. Therefore, this study shows that the SNP-induced nitrosative stress decreased Bcl-XL expression, and then induced apoptotic insults to rat osteoblasts through downregulating phosphorylation of MAPKs and subsequent activation of NFκB and AP-1.",
keywords = "Bcl-X, MAPKs, NFκB/AP-1, Nitrosative stress, Osteoblasts",
author = "Ta-Liang Chen and Gong-Jhe Wu and Chun-Sen Hsu and Tsorng-Harn Fong and Ruei-Ming Chen",
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T1 - Nitrosative stress induces osteoblast apoptosis through downregulating MAPK-mediated NFκB/AP-1 activation and subsequent Bcl-XL expression

AU - Chen, Ta-Liang

AU - Wu, Gong-Jhe

AU - Hsu, Chun-Sen

AU - Fong, Tsorng-Harn

AU - Chen, Ruei-Ming

PY - 2010/3

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N2 - During inflammation, a large amount of reactive oxygen species is produced and causes insults to osteoblasts. This study was aimed to evaluate the molecular mechanisms of sodium nitroprusside (SNP)-induced insults to rat osteoblasts. Exposure of osteoblasts, prepared from neonatal rat calvaria to SNP increased the levels of cellular nitric oxide and intracellular reactive oxygen species, and simultaneously induced apoptotic insults in concentration- or time-dependent manners. Exposure of rat osteoblasts to SNP time-dependently decreased antiapoptotic Bcl-XL messenger RNA and protein syntheses. Treatment of rat osteoblasts with SNP decreased the translocation of transcription factors nuclear factor-kappaB (NFκB) and activator protein (AP)-1 from the cytoplasm to nuclei. Sequentially, phosphorylations of the mitogen-activated protein kinases (MAPKs) of ERK1/2, JNK1/2, and p38 MAPK decreased following SNP administration. Application of ERK1 and JNK1 small interference (si)RNAs into rat osteoblasts decreased the translation of these MAPKs and synergistically enlarged SNP-caused alterations in Bcl-XL mRNA expression and cell apoptosis. Therefore, this study shows that the SNP-induced nitrosative stress decreased Bcl-XL expression, and then induced apoptotic insults to rat osteoblasts through downregulating phosphorylation of MAPKs and subsequent activation of NFκB and AP-1.

AB - During inflammation, a large amount of reactive oxygen species is produced and causes insults to osteoblasts. This study was aimed to evaluate the molecular mechanisms of sodium nitroprusside (SNP)-induced insults to rat osteoblasts. Exposure of osteoblasts, prepared from neonatal rat calvaria to SNP increased the levels of cellular nitric oxide and intracellular reactive oxygen species, and simultaneously induced apoptotic insults in concentration- or time-dependent manners. Exposure of rat osteoblasts to SNP time-dependently decreased antiapoptotic Bcl-XL messenger RNA and protein syntheses. Treatment of rat osteoblasts with SNP decreased the translocation of transcription factors nuclear factor-kappaB (NFκB) and activator protein (AP)-1 from the cytoplasm to nuclei. Sequentially, phosphorylations of the mitogen-activated protein kinases (MAPKs) of ERK1/2, JNK1/2, and p38 MAPK decreased following SNP administration. Application of ERK1 and JNK1 small interference (si)RNAs into rat osteoblasts decreased the translation of these MAPKs and synergistically enlarged SNP-caused alterations in Bcl-XL mRNA expression and cell apoptosis. Therefore, this study shows that the SNP-induced nitrosative stress decreased Bcl-XL expression, and then induced apoptotic insults to rat osteoblasts through downregulating phosphorylation of MAPKs and subsequent activation of NFκB and AP-1.

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