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Hypoxia induces apoptosis and autophagic cell death in human periodontal ligament cells through HIF-1α pathway

Cell Prolif. 2012 Jun;45(3):239-48. doi: 10.1111/j.1365-2184.2012.00810.x. Epub 2012 Mar 20.

Abstract

Objectives: Oxygen deficiency caused by occlusal trauma and smoking can be present in patients with periodontitis. However, biochemical events important in periodontal tissues during hypoxia remain unclear. The aim of this study was to investigate effects of hypoxia on apoptosis and autophagy of human periodontal ligament cells (PDLCs) in vitro.

Materials and methods: Human PDLCs were obtained and cultured in vitro. Cell viability, apoptosis, autophagy and gene and protein expression were measured in presence and absence of cobalt chloride (CoCl(2)).

Results: CoCl(2) induced cytotoxicity of human PDLCs in a concentration-dependent manner dependent on macromolecular synthesis, and resulted in apoptosis and mitochondrial dysfunction. CoCl(2) also induced redistribution of autophagy marker LC3, increased ratio of LC3-IIto LC3-Iand function of lysosomes. Furthermore, CoCl(2) promoted expression of HIF-1α following upregulation of expressions of Bnip3. Significant increases in expression of IL-1β and MMP-8 were also observed. All these results were reversed by pre-treatment with antioxidant N-acetylcysteine.

Conclusions: Our data showed that CoCl(2) could induce cytotoxicity through mitochondria- apoptotic and autophagic pathways involved in HIF-1α. CoCl(2 -treated PDLCs may serve as an in vitro model for studies of molecular mechanisms in periodontitis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimutagenic Agents / pharmacology
  • Apoptosis* / drug effects
  • Autophagy* / drug effects
  • Cell Hypoxia
  • Cell Survival
  • Cells, Cultured
  • Cobalt / pharmacology
  • Humans
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Interleukin-1beta / metabolism
  • Matrix Metalloproteinase 8 / metabolism
  • Membrane Potential, Mitochondrial / drug effects
  • Membrane Proteins / metabolism
  • Microtubule-Associated Proteins / metabolism
  • Periodontal Ligament / cytology*
  • Periodontal Ligament / metabolism
  • Proto-Oncogene Proteins / metabolism
  • Signal Transduction
  • Up-Regulation

Substances

  • Antimutagenic Agents
  • BNIP3 protein, human
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Interleukin-1beta
  • MAP1LC3A protein, human
  • Membrane Proteins
  • Microtubule-Associated Proteins
  • Proto-Oncogene Proteins
  • Cobalt
  • Matrix Metalloproteinase 8
  • cobaltous chloride