MicroRNA-1 participates in nitric oxide-induced apoptotic insults to MC3T3-E1 cells by targeting heat-shock protein-70

Yong Eng Lee, Hong-Chung Ye, Yi Ling Lin, Ruei Ming Chen

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Our previous studies showed that nitric oxide (NO) could induce osteoblast apoptosis. MicroRNA-1 (miR-1), a skeletal-and cardiac muscle-specific small non-coding RNA, contributes to the regulation of multiple cell activities. In this study, we evaluated the roles of miR-1 in NO-induced insults to osteoblasts and the possible mechanisms. Exposure of mouse MC3T3-E1 cells to sodium nitroprusside (SNP) increased amounts of cellular NO and intracellular reactive oxygen species. Sequentially, SNP decreased cell survival but induced caspase-3 activation, DNA fragmentation, and cell apoptosis. In parallel, treatment with SNP induced miR-1 expression in a time-dependent manner. Application of miR-1 antisense inhibitors to osteoblasts caused significant inhibition of SNP-induced miR-1 expression. Knocking down miR-1 concurrently attenuated SNP-induced alterations in cell morphology and survival. Consecutively, SNP time-dependently inhibited heat-shock protein (HSP)-70 messenger (m)RNA and protein expressions. A bioinformatic search predicted the existence of miR-1-specific binding elements in the 3’-untranslational region of HSP-70 mRNA. Downregulation of miR-1 expression simultaneously lessened SNP-induced inhibition of HSP-70 mRNA and protein expressions. Consequently, SNP-induced modifications in the mitochondrial membrane potential, caspase-3 activation, DNA fragmentation, and apoptotic insults were significantly alleviated by miR-1 antisense inhibitors. Therefore, this study showed that miR-1 participates in NO-induced apoptotic insults through targeting HSP-70 gene expression.

Original languageEnglish
Pages (from-to)246-255
Number of pages10
JournalInternational Journal of Biological Sciences
Volume11
Issue number3
DOIs
Publication statusPublished - Jan 15 2015

Keywords

  • Apoptosis
  • HSP-70
  • MicroRNA-1
  • Mitochondria
  • Nitric oxide

ASJC Scopus subject areas

  • Cell Biology
  • Developmental Biology
  • Molecular Biology
  • Ecology, Evolution, Behavior and Systematics
  • Applied Microbiology and Biotechnology

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