Ckip-1 Mediates P. gingivalis–Suppressed Cementoblast Mineralization

2021 ◽  
pp. 002203452110547
Author(s):  
X. Huang ◽  
L. Ma ◽  
X. Wang ◽  
H. Wang ◽  
Y. Peng ◽  
...  
Keyword(s):  
Incubation Time ◽  
Underlying Mechanism ◽  
Akt Signaling ◽  
Wild Type ◽  
Interacting Protein ◽  
Mitogen Activated Protein Kinases ◽  
Cell Functions ◽  
Mitogen Activated Protein ◽  
Wnt Pathways ◽  
Periapical Periodontitis

Porphyromonas gingivalis is responsible for the destruction of cementum in patients with periodontitis and periapical periodontitis. However, research about the effects of P. gingivalis on cementoblast mineralization and the underlying mechanism is still lacking. Casein kinase 2 interacting protein 1 (Ckip-1) is a scaffold protein that interacts with various proteins and signals to regulate different cell functions, such as cell morphology, apoptosis, and differentiation. In this study, we verified the suppressive effects of P. gingivalis and lipopolysaccharide (Pg-LPS) on OCCM-30 mineralization. We also showed that Ckip-1 gradually decreased during OCCM-30 mineralization but increased with the aggravation of Pg-induced inflammation. However, it remained unchanged when cells were stimulated with Pg-LPS, regardless of the concentration and incubation time. Then, more cellular cementum and enhanced Osterix expression were observed in Ckip-1 knockout mice when compared with the wild-type mice. Meanwhile, Ckip-1 silencing significantly enhanced cementoblast mineralization with or without P. gingivalis–associated inflammation. The trend was opposite when Ckip-1 was overexpressed. Finally, we found that the p38, Akt, and Wnt pathways were activated, while the Erk1/2 pathway was inhibited when Ckip-1 was silenced. The opposite results were also observed in the Ckip-1 overexpression group. Furthermore, we proved that cell mineralization was weakened when p38, Akt inhibitors were applied and strengthened when the Erk1/2 pathway was inhibited. In summary, Ckip-1 is upregulated under P. gingivalis–induced inflammation and negatively regulates cementoblast mineralization partially through mitogen-activated protein kinases and Akt signaling pathways, which may contribute to the restoration of cementum destroyed by P. gingivalis.

scholarly journals MAP Kinases and Prostate Cancer

2012 ◽  
Vol 2012 ◽  
pp. 1-9 ◽  
Author(s):  
Gonzalo Rodríguez-Berriguete ◽  
Benito Fraile ◽  
Pilar Martínez-Onsurbe ◽  
Gabriel Olmedilla ◽  
Ricardo Paniagua ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Map Kinases ◽  
Tumor Promotion ◽  
Metastatic Potential ◽  
Mitogen Activated Protein Kinases ◽  
Signal Transducers ◽  
Cell Functions ◽  
Growing Body ◽  
Mitogen Activated Protein ◽  
Androgen Independent

The three major mitogen-activated protein kinases (MAPKs) p38, JNK, and ERK are signal transducers involved in a broad range of cell functions including survival, apoptosis, and cell differentiation. Whereas JNK and p38 have been generally linked to cell death and tumor suppression, ERK plays a prominent role in cell survival and tumor promotion, in response to a broad range of stimuli such as cytokines, growth factors, ultraviolet radiation, hypoxia, or pharmacological compounds. However, there is a growing body of evidence supporting that JNK and p38 also contribute to the development of a number of malignances. In this paper we focus on the involvement of the MAPK pathways in prostate cancer, including the less-known ERK5 pathway, as pro- or antitumor mediators, through their effects on apoptosis, survival, metastatic potential, and androgen-independent growth.

scholarly journals RICK Promotes Inflammation and Lethality after Gram-Negative Bacterial Infection in Mice Stimulated with Lipopolysaccharide

2009 ◽  
Vol 77 (4) ◽  
pp. 1569-1578 ◽  
Author(s):  
Jong-Hwan Park ◽  
Yun-Gi Kim ◽  
Gabriel Núñez
Keyword(s):  
Protein Kinase ◽  
Regulatory Protein ◽  
Mitogen Activated Protein Kinase ◽  
Gram Negative Bacteria ◽  
Wild Type ◽  
Proinflammatory Response ◽  
Interacting Protein ◽  
Gram Negative ◽  
Mitogen Activated Protein

ABSTRACT RICK (receptor-interacting protein-like interacting caspase-like apoptosis regulatory protein kinase), a serine-threonine kinase, functions downstream of the pattern recognition receptors Nod1 and Nod2 to mediate NF-κB and mitogen-activated protein kinase (MAPK) activation in response to specific microbial stimuli. However, the function of RICK in the recognition and host defense of gram-negative bacteria remains poorly understood. We report here that infection of wild-type and RICK-deficient macrophages with Pseudomonas aeruginosa and Escherichia coli elicited comparable activation of NF-κB and MAPKs as well as secretion of proinflammatory cytokines. However, production of interleukin 6 (IL-6) and IL-1β induced by these gram-negative bacteria was impaired in RICK-deficient macrophages when the cells had previously been stimulated with lipopolysaccharide (LPS) or E. coli. The diminished proinflammatory response of RICK-deficient macrophages to bacteria was associated with reduced activation of NF-κB and MAPKs. Importantly, mutant mice deficient in RICK were less susceptible than wild-type mice to P. aeruginosa infection when the animals had previously been stimulated with LPS. The reduced lethality of RICK-deficient mice infected with P. aeruginosa was independent of pathogen clearance but was associated with diminished production of proinflammatory molecules in vivo. These results demonstrate that RICK contributes to the induction of proinflammatory responses and susceptibility to gram-negative bacteria after exposure to LPS, a condition that is associated with reduced Toll-like receptor signaling.

scholarly journals Protein Kinase PKR-Dependent Activation of Mitogen-Activated Protein Kinases Occurs through Mitochondrial Adapter IPS-1 and Is Antagonized by Vaccinia Virus E3L

2009 ◽  
Vol 83 (11) ◽  
pp. 5718-5725 ◽  
Author(s):  
Ping Zhang ◽  
Jeffrey O. Langland ◽  
Bertram L. Jacobs ◽  
Charles E. Samuel
Keyword(s):  
Protein Kinase ◽  
Vaccinia Virus ◽  
Protein Kinases ◽  
Signal Transduction Pathway ◽  
Mutant Virus ◽  
Wild Type ◽  
Necrosis Factor Alpha ◽  
Mitogen Activated Protein Kinases ◽  
Receptor Signal ◽  
Mitogen Activated Protein

ABSTRACT The p38 and c-Jun N-terminal kinase (JNK) mitogen-activated protein kinases (MAPKs) play important roles in the host innate immune response. The protein kinase regulated by RNA (PKR) is implicated in p38 MAPK activation in response to proinflammatory signals in mouse embryonic fibroblasts. To test the role of PKR in the activation of p38 and JNK MAPKs in human cells following viral infection, HeLa cells made stably deficient in PKR by using an RNA interference strategy were compared to cells with sufficient PKR. The phosphorylation of both p38 and JNK in cells with sufficient PKR was activated following either infection with an E3L deletion (ΔE3L) mutant of vaccinia virus or transfection with double-stranded RNA (dsRNA) in the absence of infection with wild-type vaccinia virus. The depletion of PKR by stable knockdown impaired the phosphorylation of both p38 and JNK induced by either the ΔE3L mutant virus or dsRNA but not that induced by tumor necrosis factor alpha. The PKR-dependent activation of MAPKs in ΔE3L mutant-infected cells was abolished by treatment with cytosine β-d-arabinoside. The complementation of PKR-deficient cells with the human PKR wild-type protein, but not with the PKR catalytic mutant (K296R) protein, restored p38 and JNK phosphorylation following ΔE3L mutant virus infection. Transient small interfering RNA knockdown established that the p38 and JNK kinase activation following ΔE3L infection was dependent upon RIG-I-like receptor signal transduction pathway components, including the mitochondrial adapter IPS-1 protein.

Silibinin Protects against Photocarcinogenesis via Modulation of Cell Cycle Regulators, Mitogen-Activated Protein Kinases, and Akt Signaling

2004 ◽  
Vol 64 (17) ◽  
pp. 6349-6356 ◽  
Author(s):  
Gu Mallikarjuna ◽  
Sivanandhan Dhanalakshmi ◽  
Rana P. Singh ◽  
Chapla Agarwal ◽  
Rajesh Agarwal
Keyword(s):  
Cell Cycle ◽  
Protein Kinases ◽  
Akt Signaling ◽  
Cell Cycle Regulators ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

scholarly journals Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL) Induces Rheumatoid Arthritis Synovial Fibroblast Proliferation through Mitogen-activated Protein Kinases and Phosphatidylinositol 3-Kinase/Akt

2005 ◽  
Vol 280 (16) ◽  
pp. 15709-15718 ◽  
Author(s):  
Jacques Morel ◽  
Rachel Audo ◽  
Michael Hahne ◽  
Bernard Combe
Keyword(s):  
Rheumatoid Arthritis ◽  
Tumor Necrosis Factor ◽  
Protein Kinases ◽  
Tumor Necrosis ◽  
Akt Signaling ◽  
Phosphatidylinositol 3 Kinase ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein ◽  
Necrosis Factor ◽  
Phosphatidylinositol 3

A hallmark of rheumatoid arthritis (RA) is the pseudo-tumoral expansion of fibroblast-like synoviocytes (FLSs), and the RA FLS has therefore been proposed as a therapeutic target. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) has been described as a pro-apoptotic factor on RA FLSs and, therefore, suggested as a potential drug. Here we report that exposure to TRAIL-induced apoptosis in a portion (up to 30%) of RA FLSs within the first 24 h. In the cells that survived, TRAIL induced RA FLS proliferation in a dose-dependent manner, with maximal proliferation observed at 0.25 nm. This was blocked by a neutralizing anti-TRAIL antibody. RA FLSs were found to express constitutively TRAIL receptors 1 and 2 (TRAIL-R1 and TRAIL-R2) on the cell surface. TRAIL-R2 appears to be the main mediator of TRAIL-induced stimulation, as RA FLS proliferation induced by an agonistic anti-TRAIL-R2 antibody was comparable with that induced by TRAIL. TRAIL activated the mitogen-activated protein kinases ERK and p38, as well as the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway with kinetics similar to those of TNF-α. Moreover, TRAIL-induced RA FLS proliferation was inhibited by the protein kinase inhibitors PD98059, SB203580, and LY294002, confirming the involvement of the ERK, p38, and PI3 kinase/Akt signaling pathways. This dual functionality of TRAIL in stimulating apoptosis and proliferation has important implications for its use in the treatment of RA.

scholarly journals Regulation of the Mitogen-Activated Protein Kinases by Brucella spp. Expressing a Smooth and Rough Phenotype: Relationship to Pathogen Invasiveness

2005 ◽  
Vol 73 (5) ◽  
pp. 3178-3183 ◽  
Author(s):  
María P. Jiménez de Bagüés ◽  
Antoine Gross ◽  
Annie Terraza ◽  
Jacques Dornand
Keyword(s):  
Protein Kinase ◽  
Protein Kinases ◽  
Host Defense ◽  
Mitogen Activated Protein Kinase ◽  
Wild Type ◽  
Immune Intervention ◽  
Mitogen Activated Protein Kinases ◽  
Mapk Pathways ◽  
Immune Mediators ◽  
Mitogen Activated Protein

ABSTRACT By comparing smooth wild-type Brucella spp. to their rough mutants, we show that the LPS O chain restricted the activation of the ERK1/2 and p38 mitogen-activated protein kinase (MAPK) pathways, thus preventing the synthesis of immune mediators that regulate host defense. We conclude that the MAPKs are a target for immune intervention by virulent smooth Brucella.

scholarly journals GLCCI1 Deficiency Induces Glucocorticoid Resistance via the Competitive Binding of IRF1:GRIP1 and IRF3:GRIP1 in Asthma

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinyue Hu ◽  
Shuanglinzi Deng ◽  
Lisha Luo ◽  
Yuanyuan Jiang ◽  
Huan Ge ◽  
...  
Keyword(s):  
Epithelial Cells ◽  
Glucocorticoid Receptor ◽  
Significant Role ◽  
Airway Hyperresponsiveness ◽  
A549 Cells ◽  
Underlying Mechanism ◽  
Wild Type ◽  
Dexamethasone Treatment ◽  
Interacting Protein ◽  
The Individual

GLCCI1 plays a significant role in modulating glucocorticoid (GC) sensitivity in asthma. This project determines the underlying mechanism that GLCCI1 deficiency attenuates GC sensitivity in dexamethasone (Dex)-treated Ovalbumin (OVA)-induced asthma mice and epithelial cells through upregulating binding of IRF1:GRIP1 and IRF3:GRIP1. Dexamethasone treatment led to less reduced inflammation, airway hyperresponsiveness, and activation of the components responsible for GC activity, as determined by decreased GR and glucocorticoid receptor interacting protein 1 (GRIP1) expression but augmented IRF1 and IRF3 expression in GLCCI1−/− asthmatic mice compared with wild type asthmatic mice. Moreover, the recruitment of GRIP1 to GR was downregulated, while the individual recruitment of GRIP1 to IRF1 and IRF3 was upregulated in GLCCI1−/− Dex-treated asthmatic mice compared to wild type Dex-treated asthmatic mice. We also found that GLCCI1 knockdown reduced GR and GRIP1 expression but increased IRF1 and IRF3 expression in Beas2B and A549 cells. Additionally, GLCCI1 silencing increased the interactions between GRIP1 with IRF1 and GRIP1 with IRF3, but decreased the recruitment of GRIP1 to GR. These studies support a critical but previously unrecognized effect of GLCCI1 expression on epithelial cells in asthma GC responses by which GLCCI1 deficiency reduces the GR and GRIP1 interaction but competitively enhances the recruitment of GRIP1 to IRF1 and IRF3.

scholarly journals H2S Persulfidated and Increased Kinase Activity of MPK4 to Response Cold Stress in Arabidopsis

2021 ◽  
Vol 8 ◽  
Author(s):  
Xinzhe Du ◽  
Zhuping Jin ◽  
Zhiqiang Liu ◽  
Danmei Liu ◽  
Liping Zhang ◽  
...  
Keyword(s):  
Cold Stress ◽  
Stress Resistance ◽  
Kinase Activity ◽  
Carbon Oxide ◽  
Underlying Mechanism ◽  
Activity Level ◽  
Biotic And Abiotic Stress ◽  
Plant Growth And Development ◽  
Mitogen Activated Protein Kinases ◽  
Mitogen Activated Protein

Hydrogen sulfide (H2S) is a gasotransmitter along with nitric oxide and carbon oxide, which is involved in plant growth and development as well as biotic and abiotic stress resistance. In a previous study, we reported that mitogen-activated protein kinases, especially MPK4, are important downstream components of H2S involved in alleviating cold stress; however the underlying mechanism is unclear. In this study, we determined that the ability of H2S to alleviate cold stress is impaired in mpk4 mutants, but not in the upstream mek2 and crlk1 mutants. MPK4 was basically persulfidated, and NaHS (H2S donor) further increased the persulfidation level of MPK4. MEK2 was not persulfidated by H2S. NaHS treatments increased the MPK4 activity level nearly tenfold. The persulfidation signal of MPK4 did not disappear after eight cystein residues in MPK4 were site-mutated, respectively. Above all, our results suggested that H2S alleviates cold stress directly by persulfidating MPK4 and increasing the MPK4 kinase activity.

Sign in / Sign up

Export Citation Format

Share Document