Porphyromonas gingivalis infection sequesters pro-apoptotic Bad through Akt in primary gingival epithelial cells

L. Yao, C. Jermanus, B. Barbetta, C. Choi, P. Verbeke, D. M. Ojcius, Ö Yilmaz*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

107 Scopus citations

Abstract

Porphyromonas gingivalis, a self-limiting oral pathogen, can colonize and replicate in gingival epithelial cells (GECs). P. gingivalis-infected GECs are protected from mitochondrion-dependent apoptosis, partially through activation of phosphatidyl inositol 3-kinase/Akt signaling. Biochemical events associated with P. gingivalis-induced inhibition of apoptosis include the blocking of mitochondrial membrane permeability and cytochrome-c release. We studied functional importance of Akt and the status of associated key mitochondrial molecules, pro-apoptotic Bad and caspase-9, during infection of GECs. We found that P. gingivalis infection caused significant phosphorylation of Bad progressively, while messenger RNA levels for Bad slowly decreased. Fluorescence microscopy showed translocation of the mitochondrial Bad to the cytosol post-infection. Conversely, P. gingivalis lost the ability to promote phosphorylation and translocation of Bad in Akt-deficient GECs. Caspase-9 activation induced by a chemical inducer of apoptosis was significantly inhibited by infection over time. However, Akt depletion by small interfering RNA did not reverse inhibition of caspase-9 activation by infection. Hence, P. gingivalis inactivates pro-apoptotic Bad through Akt. The inhibition of caspase-9 activation appears to be independent of Akt. Overall, our findings suggest that Akt is a key component of anti-apoptotic pathways stimulated by P. gingivalis. The P. gingivalis uses other mitochondrial pathways to protect host cells from cell-death and to ensure its survival in gingival epithelium.

Original languageEnglish
Pages (from-to)89-101
Number of pages13
JournalMolecular Oral Microbiology
Volume25
Issue number2
DOIs
StatePublished - 04 2010
Externally publishedYes

Keywords

  • Apoptosis
  • Cell survival
  • Mitochondria
  • Persistence
  • Porphyromonas

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