Evidence map›Paper›PMID 25564612›Full record

ArticleThe Journal of biological chemistry2015

Attenuation of the phosphatidylinositol 3-kinase/Akt signaling pathway by Porphyromonas gingivalis gingipains RgpA, RgpB, and Kgp.

Masaaki Nakayama, Tetsuyoshi Inoue, Mariko Naito, Koji Nakayama, Naoya Ohara

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.

0numbers the graph read from it
0cells of the map it votes in
36citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

36 citing papers in PubMed, 66 citations in OpenAlex.

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  17. Microbiome-mediated incapacitation of interferon lambda production in the oral mucosa.Proceedings of the National Academy of Sciences of the United States of America · 2021
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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

5 authors at 2 institutions in 1 country.

Masaaki NakayamaFrom the Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and; the Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University, Okayama 700-8558 and.
Tetsuyoshi InoueFrom the Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and; the Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University, Okayama 700-8558 and.
Mariko Naitothe Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan.
Koji Nakayamathe Division of Microbiology and Oral Infection, Department of Molecular Microbiology and Immunology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, 852-8588, Japan.
Naoya OharaFrom the Department of Oral Microbiology, Graduate School of Medicine, Dentistry and Pharmaceutical Sciences and; the Advanced Research Center for Oral and Craniofacial Sciences, Dental School, Okayama University, Okayama 700-8558 and. Electronic address: oharan@md.okayama-u.ac.jp.
Okayama University · JPNagasaki University · JP

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Porphyromonas gingivalis is a major pathogen of periodontal diseases, including periodontitis. We have investigated the effect of P. gingivalis infection on the PI3K/Akt (protein kinase B) signaling pathway in gingival epithelial cells. Here, we found that live P. gingivalis, but not heat-killed P. gingivalis, reduced Akt phosphorylation at both Thr-308 and Ser-473, which implies a decrease in Akt activity. Actually, PI3K, which is upstream of Akt, was also inactivated by P. gingivalis. Furthermore, glycogen synthase kinase 3α/β, mammalian target of rapamycin, and Bad, which are downstream proteins in the PI3K/Akt cascade, were also dephosphorylated, a phenomenon consistent with Akt inactivation by P. gingivalis. However, these events did not require direct interaction between bacteria and host cells and were independent of P. gingivalis invasion into the cells. The use of gingipain-specific inhibitors and a gingipain-deficient P. gingivalis mutant KDP136 revealed that the gingipains and their protease activities were essential for the inactivation of PI3K and Akt. The associations between the PI3K regulatory subunit p85α and membrane proteins were disrupted by wild-type P. gingivalis. Moreover, PDK1 translocation to the plasma membrane was reduced by wild-type P. gingivalis, but not KDP136, indicating little production of phosphatidylinositol 3,4,5-triphosphate by PI3K. Therefore, it is likely that PI3K failed to transmit homeostatic extracellular stimuli to intracellular signaling pathways by gingipains. Taken together, our findings indicate that P. gingivalis attenuates the PI3K/Akt signaling pathway via the proteolytic effects of gingipains, resulting in the dysregulation of PI3K/Akt-dependent cellular functions and the destruction of epithelial barriers.

Indexed as

Adhesins, BacterialBacteroidaceae Infectionsbcl-Associated Death ProteinCell LineCysteine EndopeptidasesGingipain Cysteine EndopeptidasesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaHumansMutationPeriodontitisPhosphatidylinositol 3-KinasesPorphyromonas gingivalisProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinaseAdhesins, BacterialBAD protein, humanbcl-Associated Death ProteinCysteine EndopeptidasesGingipain Cysteine EndopeptidasesGlycogen Synthase Kinase 3Glycogen Synthase Kinase 3 betaMTOR protein, humanPDK1 protein, humanPhosphatidylinositol 3-KinasesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktPyruvate Dehydrogenase Acetyl-Transferring KinaseTOR Serine-Threonine KinasesAkt PKBGingipainPhosphatidylinositide 3-Kinase (PI 3-Kinase)Porphyromonas gingivalisProteolysisSignal TransductionVirulence Factor

Identifiers

PMID25564612
PMCPMC4335252
OpenAlexW2035298743

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.