scholarly journals Acanthus ilicifolius L. Treatment for Oral Candidiasis with Immunosuppressive Conditions Subjected to p38 MAPK Enhancement

2021 ◽  
Vol 16 (Supp. 1) ◽  
pp. 17-24
Author(s):  
Dwi Andriani ◽  
Agni Febrina Pargaputri ◽  
Kristanti Parisihni ◽  
Syamsulina Revianti
Keyword(s):  
P38 Mapk ◽  
Potent Inhibitor ◽  
Methanolic Extract ◽  
Oral Candidiasis ◽  
Mitogen Activated Protein Kinase ◽  
Immunohistochemical Examination ◽  
Acanthus Ilicifolius ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
One Way Anova

Methanolic extract from the leaves of Acanthus ilicifolius L. (A. ilicifolius L.) is a potent inhibitor of Candida albicans (C. albicans) growth and anti-inflammatory. C. albicans causes oral candidiasis in immunosuppressive condition. Mitogen-activated protein kinase (MAPK) signalling via p38 appears to discriminate between yeast and hyphal cells of C. albicans. Activation of p38 MAPK by hyphae results in the upregulation of proinflammatory cytokines. The p38 MAPK activation is known to impair corticosteroid action. The research was conducted to investigate the effect of methanolic extract A. ilicifolius L. treatment of oral candidiasis with the immunosuppressive condition through enhancement of p38 MAPK expression in the epithelial cells. Immunosuppressed conditions were obtained when 16 healthy male Rattus norvergicus (Wistar) was given oral administration of dexamethasone and tetracycline for 14 days and induced with C. albicans (ATCC-10231) 1 McFarland. The subjects were divided into four groups (n = 4/group): immunosuppression (IS), immunosuppression with oral candidiasis without treatment (ISC), immunosuppression with oral candidiasis and nystatin treatment (ISC+N), and immunosuppression with oral candidiasis and A. ilicifolius L. treatment (ISC+AI), and were treated for 14 days. Later, the rats were euthanised, and their tongue were biopsied. The p38 MAPK expression was subjected to immunohistochemical examination, observed under a microscope (400× magnification) and statistically analysed (one-way ANOVA, LSD-test, p < 0.05). The p38 MAPK expression of ISC+AI (36.05 ± 1.54) was higher than IS (26 ± 2.32), ISC (26.4 ± 3.71), IS+N (34.2 ± 0.99). Significant differences existed between ISC+AI and ISC+N to IS and ISC (p < 0.05). No significant differences were present between IS and ISC; ISC+AI and ISC+N (p > 0.05). Therefore, this treatment could enhance p38 MAPK expression in oral candidiasis with the immunosuppressed condition.

scholarly journals The Role of p38 MAPK and Its Substrates in Neuronal Plasticity and Neurodegenerative Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-12 ◽  
Author(s):  
Sônia A. L. Corrêa ◽  
Katherine L. Eales
Keyword(s):  
Neurodegenerative Diseases ◽  
P38 Mapk ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Mechanisms ◽  
Cellular Localisation ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Normal Ageing ◽  
Actin Remodelling

A significant amount of evidence suggests that the p38-mitogen-activated protein kinase (MAPK) signalling cascade plays a crucial role in synaptic plasticity and in neurodegenerative diseases. In this review we will discuss the cellular localisation and activation of p38 MAPK and the recent advances on the molecular and cellular mechanisms of its substrates: MAPKAPK 2 (MK2) and tau protein. In particular we will focus our attention on the understanding of the p38 MAPK-MK2 and p38 MAPK-tau activation axis in controlling neuroinflammation, actin remodelling and tau hyperphosphorylation, processes that are thought to be involved in normal ageing as well as in neurodegenerative diseases. We will also give some insight into how elucidating the precise role of p38 MAPK-MK2 and p38 MAPK-tau signalling cascades may help to identify novel therapeutic targets to slow down the symptoms observed in neurodegenerative diseases such as Alzheimer's and Parkinson's disease.

Mechanisms and functions of p38 MAPK signalling

2010 ◽  
Vol 429 (3) ◽  
pp. 403-417 ◽  
Author(s):  
Ana Cuadrado ◽  
Angel R. Nebreda
Keyword(s):  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Biological Effects ◽  
Mitogen Activated Protein Kinase ◽  
Wide Range ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
External Signals ◽  
Protein Kinase Signalling ◽  
Genetic Mouse Models

The p38 MAPK (mitogen-activated protein kinase) signalling pathway allows cells to interpret a wide range of external signals and respond appropriately by generating a plethora of different biological effects. The diversity and specificity in cellular outcomes is achieved with an apparently simple linear architecture of the pathway, consisting of a core of three protein kinases acting sequentially. In the present review, we dissect the molecular mechanisms underlying p38 MAPK functions, with special emphasis on the activation and regulation of the core kinases, the interplay with other signalling pathways and the nature of p38 MAPK substrates as a source of functional diversity. Finally, we discuss how genetic mouse models are facilitating the identification of physiological functions for p38 MAPKs, which may impinge on their eventual use as therapeutic targets.

scholarly journals p38δMAPK: Emerging Roles of a Neglected Isoform

2014 ◽  
Vol 2014 ◽  
pp. 1-12 ◽  
Author(s):  
Carol O’Callaghan ◽  
Liam J. Fanning ◽  
Orla P. Barry
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Molecular Mechanisms ◽  
Mitogen Activated Protein Kinase ◽  
Biological Processes ◽  
Cellular Processes ◽  
Mapk Activity ◽  
Pathological Conditions ◽  
Mapk Signalling ◽  
Mitogen Activated Protein

p38δmitogen activated protein kinase (MAPK) is a unique stress responsive protein kinase. While the p38 MAPK family as a whole has been implicated in a wide variety of biological processes, a specific role for p38δMAPK in cellular signalling and its contribution to both physiological and pathological conditions are presently lacking. Recent emerging evidence, however, provides some insights into specific p38δMAPK signalling. Importantly, these studies have helped to highlight functional similarities as well as differences between p38δMAPK and the other members of the p38 MAPK family of kinases. In this review we discuss the current understanding of the molecular mechanisms underlying p38δMAPK activity. We outline a role for p38δMAPK in important cellular processes such as differentiation and apoptosis as well as pathological conditions such as neurodegenerative disorders, diabetes, and inflammatory disease. Interestingly, disparate roles for p38δMAPK in tumour development have also recently been reported. Thus, we consider evidence which characterises p38δMAPK as both a tumour promoter and a tumour suppressor. In summary, while our knowledge of p38δMAPK has progressed somewhat since its identification in 1997, our understanding of this particular isoform in many cellular processes still strikingly lags behind that of its counterparts.

ERK5 and its role in tumour development

2012 ◽  
Vol 40 (1) ◽  
pp. 251-256 ◽  
Author(s):  
Pamela A. Lochhead ◽  
Rebecca Gilley ◽  
Simon J. Cook
Keyword(s):  
Mitogen Activated Protein Kinase ◽  
Invasion And Migration ◽  
Extracellular Signal Regulated Kinase ◽  
Protein Levels ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Tumour Cell Invasion ◽  
And Migration

The MEK5 [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated kinase) kinase 5]/ERK5 pathway is the least well studied MAPK signalling module. It has been proposed to play a role in the pathology of cancer. In the present paper, we review the role of the MEK5/ERK5 pathway using the ‘hallmarks of cancer’ as a framework and consider how this pathway is deregulated. As well as playing a key role in endothelial cell survival and tubular morphogenesis during tumour neovascularization, ERK5 is also emerging as a regulator of tumour cell invasion and migration. Several oncogenes can stimulate ERK5 activity, and protein levels are increased by a novel amplification at chromosome locus 17p11 and by down-regulation of the microRNAs miR-143 and miR-145. Together, these finding underscore the case for further investigation into understanding the role of ERK5 in cancer.

scholarly journals Exercise-induced mitogen-activated protein kinase signalling in skeletal muscle

2004 ◽  
Vol 63 (2) ◽  
pp. 227-232 ◽  
Author(s):  
Yun Chau Long ◽  
Ulrika Widegren ◽  
Juleen R. Zierath
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Muscle Contraction ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Cascades ◽  
Extracellular Signal ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Exercise Induced ◽  
Response To Exercise

Exercise training improves glucose homeostasis through enhanced insulin sensitivity in skeletal muscle. Muscle contraction through physical exercise is a physiological stimulus that elicits multiple biochemical and biophysical responses and therefore requires an appropriate control network. Mitogen-activated protein kinase (MAPK) signalling pathways constitute a network of phosphorylation cascades that link cellular stress to changes in transcriptional activity. MAPK cascades are divided into four major subfamilies, including extracellular signal-regulated kinases 1 and 2, p38 MAPK, c-Jun NH2-terminal kinase and extracellular signal-regulated kinase 5. The present review will present the current understanding of parallel MAPK signalling in human skeletal muscle in response to exercise and muscle contraction, with an emphasis on identifying potential signalling mechanisms responsible for changes in gene expression.

scholarly journals Effect of Novel Marine Nutraceuticals on IL-1α-Mediated TNF-αRelease from UVB-Irradiated Human Melanocyte-Derived Cells

2011 ◽  
Vol 2011 ◽  
pp. 1-11 ◽  
Author(s):  
Visalini Muthusamy ◽  
Lynn D. Hodges ◽  
Theodore A. Macrides ◽  
Glen M. Boyle ◽  
Terrence J. Piva
Keyword(s):  
Antioxidant Properties ◽  
Mitogen Activated Protein Kinase ◽  
Uvb Radiation ◽  
Reactive Oxygen Species Formation ◽  
Mapk Signalling Pathway ◽  
Species Formation ◽  
Human Melanocyte ◽  
Mapk Signalling ◽  
Mitogen Activated Protein ◽  
Necrosis Factor

UV-induced inflammation and reactive oxygen species formation are involved in the development of melanoma. Natural products like 5β-scymnol and CO2-supercritical fluid extract (CO2-SFE) of mussel oil contain anti-inflammatory and antioxidant properties that may aid in reducing the deleterious effects of UV radiation. Therefore, their effect on the release of the proinflammatory cytokine, tumour necrosis factor-α(TNF-α), from UVB-irradiated human melanocytic cells was examined. Human epidermal melanocytes (HEM) and MM96L melanoma cells were exposed to UVB radiation and IL-1α. Cell viability and TNF-αlevels were determined 24 hours after-irradiation while p38 mitogen-activated protein kinase (MAPK) activation was observed at 15 min after-irradiation. Whenα-tocopherol, CO2-SFE mussel oil, and 5β-scymnol were added to the UVB-irradiated HEM cells treated with IL-1α, TNF-αlevels fell by 53%, 65%, and 76%, respectively, while no inhibition was evident in MM96L cells. This effect was not due to inhibition of the intracellular p38 MAPK signalling pathway. These compounds may be useful in preventing inflammation-induced damage to normal melanocytes.

scholarly journals Cross-talk between IRAK-4 and the NADPH oxidase1

2007 ◽  
Vol 403 (3) ◽  
pp. 451-461 ◽  
Author(s):  
Sandrine Pacquelet ◽  
Jennifer L. Johnson ◽  
Beverly A. Ellis ◽  
Agnieszka A. Brzezinska ◽  
William S. Lane ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Nadph Oxidase ◽  
P38 Mapk ◽  
Interleukin 1 ◽  
Mitogen Activated Protein Kinase ◽  
Free System ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Tlr4 Activation

Exposure of neutrophils to LPS (lipopolysaccharide) triggers their oxidative response. However, the relationship between the signalling downstream of TLR4 (Toll-like receptor 4) after LPS stimulation and the activation of the oxidase remains elusive. Phosphorylation of the cytosolic factor p47phox is essential for activation of the NADPH oxidase. In the present study, we examined the hypothesis that IRAK-4 (interleukin-1 receptor-associated kinase-4), the main regulatory kinase downstream of TLR4 activation, regulates the NADPH oxidase through phosphorylation of p47phox. We show that p47phox is a substrate for IRAK-4. Unlike PKC (protein kinase C), IRAK-4 phosphorylates p47phox not only at serine residues, but also at threonine residues. Target residues were identified by tandem MS, revealing a novel threonine-rich regulatory domain. We also show that p47phox is phosphorylated in granulocytes in response to LPS stimulation. LPS-dependent phosphorylation of p47phox was enhanced by the inhibition of p38 MAPK (mitogen-activated protein kinase), confirming that the kinase operates upstream of p38 MAPK. IRAK-4-phosphorylated p47phox activated the NADPH oxidase in a cell-free system, and IRAK-4 overexpression increased NADPH oxidase activity in response to LPS. We have shown that endogenous IRAK-4 interacts with p47phox and they co-localize at the plasma membrane after LPS stimulation, using immunoprecipitation assays and immunofluorescence microscopy respectively. IRAK-4 was activated in neutrophils in response to LPS stimulation. We found that Thr133, Ser288 and Thr356, targets for IRAK-4 phosphorylation in vitro, are also phosphorylated in endogenous p47phox after LPS stimulation. We conclude that IRAK-4 phosphorylates p47phox and regulates NADPH oxidase activation after LPS stimulation.

MKK3-p38 signaling promotes apoptosis and the early inflammatory response in the obstructed mouse kidney

2007 ◽  
Vol 293 (5) ◽  
pp. F1556-F1563 ◽  
Author(s):  
Frank Y. Ma ◽  
Greg H. Tesch ◽  
Richard A. Flavell ◽  
Roger J. Davis ◽  
David J. Nikolic-Paterson
Keyword(s):  
Inflammatory Response ◽  
P38 Mapk ◽  
Renal Injury ◽  
Mapk Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Mrna Levels ◽  
Direct Role ◽  
Mitogen Activated Protein ◽  
Early Inflammatory Response ◽  
Induced Apoptosis

Activation of the p38 mitogen-activated protein kinase (MAPK) pathway induces inflammation, apoptosis, and fibrosis. However, little is known of the contribution of the upstream kinases, MMK3 and MKK6, to activation of the p38 kinase in the kidney and consequent renal injury. This study investigated the contribution of MKK3 to p38 MAPK activation and renal injury in the obstructed kidney. Groups of eight wild-type (WT) or Mkk3−/− mice underwent unilateral ureteric obstruction (UUO) and were killed 3 or 7 days later. Western blotting showed a marked increase in phospho-p38 (p-p38) MAPK in UUO WT kidney. The same trend of increased p-p38 MAPK was seen in the UUO Mkk3−/− kidney, although the actual level of p-p38 MAPK was significantly reduced compared with WT, and this could not be entirely compensated for by the increase in MKK6 expression in the Mkk3−/− kidney. Apoptosis of tubular and interstitial cells in WT UUO mice was reduced by 50% in Mkk3−/− UUO mice. Furthermore, cultured Mkk3−/− tubular epithelial cells showed resistance to H2O2-induced apoptosis, suggesting a direct role for MKK3-p38 signaling in tubular apoptosis. Upregulation of MCP-1 mRNA levels and macrophage infiltration seen on day 3 in WT UUO mice was significantly reduced in Mkk3−/− mice, but this difference was not evident by day 7. The development of renal fibrosis in Mkk3−/− UUO mice was not different from that seen in WT UUO mice. In conclusion, these studies identify discrete roles for MKK3-p38 signaling in renal cell apoptosis and the early inflammatory response in the obstructed kidney.

scholarly journals Somatostatin stimulates intestinal NHE8 expression via p38 MAPK pathway

2011 ◽  
Vol 300 (2) ◽  
pp. C375-C382 ◽  
Author(s):  
Chunhui Wang ◽  
Hua Xu ◽  
Huacong Chen ◽  
Jing Li ◽  
Bo Zhang ◽  
...  
Keyword(s):  
P38 Mapk ◽  
Mapk Pathway ◽  
Somatostatin Receptor ◽  
Peptide Hormone ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein ◽  
D Cells ◽  
Human Intestinal Cells

Diarrhea is a common manifestation of gastrointestinal disorders. Diarrhea-induced losses of fluid and electrolyte could lead to dehydration and electrolyte imbalances, resulting in significant morbidity and mortality, especially in children living in developing countries. Somatostatin, a peptide hormone secreted by D-cells, plays an important role in regulating motility and intestinal Na+ absorption. Although octreotide, a somatostatin analog, is used to treat diarrhea, its mechanisms of action are unclear. Here we showed that octreotide increased brush-border membrane Na+/H+ exchanger 8 (NHE8) expression in the small intestine to the exclusion of other NHEs that participate in Na+ absorption. The same effect also occurred in human intestinal cells (Caco-2). We found that the increase of NHE8 expression by somatostatin required p38 mitogen-activated protein kinase (MAPK) activation. Furthermore, the somatostatin receptor SSTR2 antagonist CYN154806 could abolish somatostatin-induced NHE8 expression and p38 MAPK phosphorylation. Thus our data provided the first concrete evidence indicating that somatostatin stimulates intestinal Na+ absorption by increasing intestinal NHE8 expression through the SSTR2-p38 MAPK pathway.

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