Trypsin-like protease-active extracellular protein extracts from Porphyromonas gingivalis ATCC 33277 induce apoptosis in bovine aortic endothelial cells

J Periodontal Res. 2010 Oct;45(5):650-7. doi: 10.1111/j.1600-0765.2010.01280.x. Epub 2010 Jun 20.

Abstract

Background and objective: Certain virulence factors participating in periodontitis may relate to cardiovascular diseases. This study was to evaluate the pro-apoptotic effect of protein extracts from Porphyromonas gingivalis on bovine aortic endothelial cells (BAECs).

Material and methods: The BAECs were exposed to trypsin-like protease-active protein extracts from P. gingivalis, and apoptosis was examined by Hoechst 33342 staining, DNA fragmentation assay and cleaved caspase-3 detection. When BAECs were exposed to protein extracts pretreated with trypsin-like protease inhibitor (TLCK), the apoptosis rate was evaluated by Annexin V-propidium iodide staining. To further study the potential mechanism of the pro-apoptotic effect, immunoblotting was used to detect expression of alpha-tubulin, integrin beta1 and activated ERK1/2 in BAECs treated with protein extracts or cultured in suspension.

Results: After exposure to the protein extracts, BAECs exhibited loss of cell adhesion and apoptotic cell death. The pro-apoptotic effect could be delayed by TLCK pretreatment. In addition, BAECs treated with protein extracts showed decreased levels of alpha-tubulin, integrin beta1 and activated ERK1/2. When BAECs were cultured in suspension, ERK1/2 activation was also inhibited, but the percentage decrease in ERK1/2 activation was less than that induced by protein extracts. Moreover, no significantly altered expression of alpha-tubulin was detected in suspended cells.

Conclusion: Trypsin-like protease-active protein extracts from P. gingivalis could induce apoptosis of BAECs. The destruction of alpha-tubulin and integrin beta1 and decrease of ERK1/2 activation might contribute to the pro-apoptotic effect of the protein extracts.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta / cytology
  • Aorta / drug effects*
  • Apoptosis* / drug effects
  • Bacterial Proteins / pharmacology*
  • Cattle
  • Cell Adhesion / drug effects
  • Cells, Cultured
  • Culture Media, Conditioned / pharmacology
  • Endothelial Cells / drug effects
  • Endothelium, Vascular / cytology
  • Endothelium, Vascular / drug effects*
  • Enzyme Activation / drug effects
  • Integrin beta1 / metabolism
  • Mitogen-Activated Protein Kinases / metabolism
  • Porphyromonas gingivalis / enzymology*
  • Trypsin / pharmacology*
  • Trypsin Inhibitors / pharmacology
  • Tubulin / metabolism
  • Virulence Factors / pharmacology

Substances

  • Bacterial Proteins
  • Culture Media, Conditioned
  • Integrin beta1
  • Trypsin Inhibitors
  • Tubulin
  • Virulence Factors
  • Mitogen-Activated Protein Kinases
  • Trypsin