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*

*此作品的通信作者

研究成果: 期刊稿件文章同行評審

109 引文 斯高帕斯(Scopus)

摘要

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.

原文英語
頁(從 - 到)89-101
頁數13
期刊Molecular Oral Microbiology
25
發行號2
DOIs
出版狀態已出版 - 04 2010
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