Novel function of Porphyromonas gingivalis gingipains in the PI3K/Akt signaling pathway

Research output: Contribution to journalArticle

Abstract

Background: Porphyromonas gingivalis is s major oral bacterium closely associated with periodontal diseases including periodontitis and directly affects host cellular signaling. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays multiple roles in various cell functions including cell survival and glucose metabolism. In this review, we describe the effect of gingipains on the PI3K/Akt signaling pathway in P. gingivalis infection. Highlight: Gingipains inactivate PI3K and Akt in gingival epithelial cells infected with P. gingivalis. These events occur independently of invasion of this organism into the cells and are required for the enzymatic activity of gingipains. Furthermore, 3-Phosphoinositide-dependent protein kinase-1 (PDK1) failed to translocate to the plasma membrane from the cytosol following PI3K inactivation.Additionally, dephosphorylation of Akt downstream proteins, including glycogen synthase kinase 3 (GSK3), mammalian target of rapamycin (mTOR), and Bad, occurs in parallel with the dysregulation of PI3K/PDK1/Akt cascades. Conclusion: This review describes the biological characterization of gingipains, which inactivate PI3K and Akt, and disorder the PI3K/Akt signaling pathway. Hence, gingipains may decrease cellular physiological functions, eventually disrupting the gingival epithelium and causing development of periodontal diseases.

Original languageEnglish
JournalJournal of Oral Biosciences
DOIs
Publication statusAccepted/In press - Feb 22 2017

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Phosphatidylinositol 3-Kinase
Porphyromonas gingivalis
Periodontal Diseases
3-Phosphoinositide-Dependent Protein Kinases
Cell signaling
Glycogen Synthase Kinase 3
Periodontitis
Sirolimus
Cell membranes
Phosphatidylinositols
Porphyromonas gingivalis argingipain
Metabolism
Cytosol
Protein Kinases
Cell Survival
Bacteria
Epithelium
Epithelial Cells
Cells
Cell Membrane

Keywords

  • Gingipains
  • PI3K/Akt signaling pathway
  • Porphyromonas gingivalis
  • Virulence factors

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Dentistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Novel function of Porphyromonas gingivalis gingipains in the PI3K/Akt signaling pathway",
abstract = "Background: Porphyromonas gingivalis is s major oral bacterium closely associated with periodontal diseases including periodontitis and directly affects host cellular signaling. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays multiple roles in various cell functions including cell survival and glucose metabolism. In this review, we describe the effect of gingipains on the PI3K/Akt signaling pathway in P. gingivalis infection. Highlight: Gingipains inactivate PI3K and Akt in gingival epithelial cells infected with P. gingivalis. These events occur independently of invasion of this organism into the cells and are required for the enzymatic activity of gingipains. Furthermore, 3-Phosphoinositide-dependent protein kinase-1 (PDK1) failed to translocate to the plasma membrane from the cytosol following PI3K inactivation.Additionally, dephosphorylation of Akt downstream proteins, including glycogen synthase kinase 3 (GSK3), mammalian target of rapamycin (mTOR), and Bad, occurs in parallel with the dysregulation of PI3K/PDK1/Akt cascades. Conclusion: This review describes the biological characterization of gingipains, which inactivate PI3K and Akt, and disorder the PI3K/Akt signaling pathway. Hence, gingipains may decrease cellular physiological functions, eventually disrupting the gingival epithelium and causing development of periodontal diseases.",
keywords = "Gingipains, PI3K/Akt signaling pathway, Porphyromonas gingivalis, Virulence factors",
author = "Masaaki Nakayama and Naoya Oohara",
year = "2017",
month = "2",
day = "22",
doi = "10.1016/j.job.2017.05.003",
language = "English",
journal = "Journal of Oral Biosciences",
issn = "1349-0079",
publisher = "Japanese Association for Oral Biology",

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T1 - Novel function of Porphyromonas gingivalis gingipains in the PI3K/Akt signaling pathway

AU - Nakayama, Masaaki

AU - Oohara, Naoya

PY - 2017/2/22

Y1 - 2017/2/22

N2 - Background: Porphyromonas gingivalis is s major oral bacterium closely associated with periodontal diseases including periodontitis and directly affects host cellular signaling. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays multiple roles in various cell functions including cell survival and glucose metabolism. In this review, we describe the effect of gingipains on the PI3K/Akt signaling pathway in P. gingivalis infection. Highlight: Gingipains inactivate PI3K and Akt in gingival epithelial cells infected with P. gingivalis. These events occur independently of invasion of this organism into the cells and are required for the enzymatic activity of gingipains. Furthermore, 3-Phosphoinositide-dependent protein kinase-1 (PDK1) failed to translocate to the plasma membrane from the cytosol following PI3K inactivation.Additionally, dephosphorylation of Akt downstream proteins, including glycogen synthase kinase 3 (GSK3), mammalian target of rapamycin (mTOR), and Bad, occurs in parallel with the dysregulation of PI3K/PDK1/Akt cascades. Conclusion: This review describes the biological characterization of gingipains, which inactivate PI3K and Akt, and disorder the PI3K/Akt signaling pathway. Hence, gingipains may decrease cellular physiological functions, eventually disrupting the gingival epithelium and causing development of periodontal diseases.

AB - Background: Porphyromonas gingivalis is s major oral bacterium closely associated with periodontal diseases including periodontitis and directly affects host cellular signaling. The phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway plays multiple roles in various cell functions including cell survival and glucose metabolism. In this review, we describe the effect of gingipains on the PI3K/Akt signaling pathway in P. gingivalis infection. Highlight: Gingipains inactivate PI3K and Akt in gingival epithelial cells infected with P. gingivalis. These events occur independently of invasion of this organism into the cells and are required for the enzymatic activity of gingipains. Furthermore, 3-Phosphoinositide-dependent protein kinase-1 (PDK1) failed to translocate to the plasma membrane from the cytosol following PI3K inactivation.Additionally, dephosphorylation of Akt downstream proteins, including glycogen synthase kinase 3 (GSK3), mammalian target of rapamycin (mTOR), and Bad, occurs in parallel with the dysregulation of PI3K/PDK1/Akt cascades. Conclusion: This review describes the biological characterization of gingipains, which inactivate PI3K and Akt, and disorder the PI3K/Akt signaling pathway. Hence, gingipains may decrease cellular physiological functions, eventually disrupting the gingival epithelium and causing development of periodontal diseases.

KW - Gingipains

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KW - Porphyromonas gingivalis

KW - Virulence factors

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