scholarly journals Melanogenic Effects of Maclurin Are Mediated through the Activation of cAMP/PKA/CREB and p38 MAPK/CREB Signaling Pathways

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Young Sun Hwang ◽  
Sae Woong Oh ◽  
See-Hyoung Park ◽  
Jienny Lee ◽  
Ju Ah. Yoo ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
P38 Mapk ◽  
Adenosine Monophosphate ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Protective Agent ◽  
Protective Effects ◽  
Skin Disorders ◽  
Creb Phosphorylation

Melanogenesis is the biological process which the skin pigment melanin is synthesized to protect the skin against ultraviolet irradiation and other external stresses. Abnormal biology of melanocytes is closely associated with depigmented skin disorders such as vitiligo. In this study, we examined the effects of maclurin on melanogenesis and cytoprotection. Maclurin enhanced cellular tyrosinase activity as well as cellular melanin levels. We found that maclurin treatment increased the expression of microphthalmia-associated transcription factor (MITF), tyrosinase-related protein- (TRP-) 1, TRP-2, and tyrosinase. Mechanistically, maclurin promoted melanogenesis through cyclic adenosine monophosphate (cAMP) response element binding (CREB) protein-dependent upregulation of MITF. CREB activation was found to be mediated by p38 mitogen-activated protein kinase (MAPK) or cAMP-protein kinase A (PKA) signaling. In addition, maclurin-induced CREB phosphorylation was mediated through the activation of both the cAMP/PKA and the p38 MAPK signaling pathways. Maclurin-induced suppression of p44/42 MAPK activation also contributed to its melanogenic activity. Furthermore, maclurin showed protective effects against H2O2 treatment and UVB irradiation in human melanocytes. These findings indicate that the melanogenic effects of maclurin depend on increased MITF gene expression, which is mediated by the activation of both p38 MAPK/CREB and cAMP/PKA/CREB signaling. Our results thus suggest that maclurin could be useful as a protective agent against hypopigmented skin disorders.

Panax notoginseng Saponins Modulate the Inflammatory Response and Improve IBD-Like Symptoms via TLR/NF-κB and MAPK Signaling Pathways

2021 ◽  
pp. 1-15
Author(s):  
Hua Luo ◽  
Chi Teng Vong ◽  
Dechao Tan ◽  
Jinming Zhang ◽  
Hua Yu ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathways ◽  
Inflammatory Responses ◽  
Panax Notoginseng ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Clinical Effects ◽  
Protective Effects ◽  
Panax Notoginseng Saponins

Panax notoginseng saponins (PNS) are the main active ingredients of Panax notoginseng (Burk) F. H. Chen, which are used as traditional Chinese medicine for thousands of years and have various clinical effects, including anti-inflammation, anti-oxidation, and cardiovascular protection. Inflammatory bowel disease (IBD) is a complex gastrointestinal inflammatory disease that cannot be cured completely nowadays. The anti-inflammatory and protective effects of PNS were analyzed in vitro and in dextran sulfate sodium (DSS)-induced colitis mouse model. PNS inhibited the release of nitric oxide (NO), tumor necrosis factor-[Formula: see text] (TNF-[Formula: see text], interleukin-6 (IL-6), and monocyte chemoattractant protein-1 (MCP-1) in Pam3CSK4-induced RAW 264.7 macrophages. In the animal study, compared with DSS-induced mice, PNS reduced the expression of pro-inflammatory cytokines (TNF-[Formula: see text], IL-6, and MCP-1) in the colon tissues. Furthermore, PNS treatment led to a remarkable reduction in the activation of the inhibitor of nuclear factor kappa-B kinase [Formula: see text]/[Formula: see text] (IKK[Formula: see text]/[Formula: see text], I[Formula: see text]B[Formula: see text] and p65 induced by DSS. On the other hand, PNS inhibited the phosphorylation of c-Jun N-terminal kinase (JNK), p38, and extracellular regulated protein kinase 1/2 (ERK1/2). Taken together, our results suggested that PNS conferred profound protection for colitis mice through the downregulation of mitogen-activated protein kinase (MAPK) and NF-[Formula: see text]B signaling pathways, which were associated with reducing inflammatory responses, alleviating tissue damage, and maintaining of intestinal integrity and functionality.

scholarly journals Glucose-Dependent Insulinotropic Polypeptide Promotes β-(INS-1) Cell Survival via Cyclic Adenosine Monophosphate-Mediated Caspase-3 Inhibition and Regulation of p38 Mitogen-Activated Protein Kinase

Endocrinology ◽  
2003 ◽  
Vol 144 (10) ◽  
pp. 4433-4445 ◽  
Author(s):  
Jan A. Ehses ◽  
Vanbric R. Casilla ◽  
Tim Doty ◽  
J. Andrew Pospisilik ◽  
Kyle D. Winter ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cell Survival ◽  
Cell Fate ◽  
P38 Mapk ◽  
Caspase 3 ◽  
Glucose Deprivation ◽  
Adenosine Monophosphate ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mapk Phosphorylation

The incretin glucose-dependent insulinotropic polypeptide (GIP) is a major regulator of postprandial insulin secretion in mammals. Recent studies in our laboratory, and others have suggested that GIP is a potent stimulus for protein kinase activation, including the MAPK (ERK1/2) module. Based on these studies, we hypothesized that GIP could regulate cell fate and sought to examine the underlying mechanisms involved in GIP stimulation of cell survival. GIP potentiated glucose-induced β-(INS-1)-cell growth to levels comparable with GH and GLP-1 while promoting cell survival in the face of serum and glucose-deprivation or treatment with wortmannin or streptozotocin. In the absence of GIP, 50% of cells died after 48 h of serum and glucose withdrawal, whereas 91 ± 10% of cells remained viable in the presence of GIP [n = 3, P < 0.05; EC50 of 1.24 ± 0.48 nm GIP (n = 4)]. Effects of GIP on cell survival and inhibition of caspase-3 were mimicked by forskolin, but pharmacological experiments excluded roles for MAPK kinase (Mek)1/2, phosphatidylinositol 3-kinase, protein kinase A, Epac, and Rap 1. Survival effects of GIP were ablated by the inhibitor SB202190, indicating a role for p38 MAPK. Furthermore, caspase-3 activity was also regulated by p38 MAPK, with a lesser role for Mek1/2, based on RNA interference studies. We propose that GIP is able to reverse caspase-3 activation via inhibition of long-term p38 MAPK phosphorylation in response to glucose deprivation (±wortmannin). Intriguingly, these findings contrasted with short-term phosphorylation of MKK3/6→p38 MAPK→ATF-2 by GIP. Thus, these data suggest that GIP is able to regulate INS-1 cell survival by dynamic control of p38 MAPK phosphorylation via cAMP signaling and lend further support to the notion that GIP regulation of MAPK signaling is critical for its regulation of cell fate.

scholarly journals APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway

2011 ◽  
Vol 300 (1) ◽  
pp. E103-E110 ◽  
Author(s):  
Xiaoban Xin ◽  
Lijun Zhou ◽  
Caleb M. Reyes ◽  
Feng Liu ◽  
Lily Q. Dong
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Adaptor Protein ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Scaffolding Protein ◽  
Mapk Activation ◽  
P38 Mapk Pathway ◽  
Mitogen Activated Protein

The adaptor protein APPL1 mediates the stimulatory effect of adiponectin on p38 mitogen-activated protein kinase (MAPK) signaling, yet the underlying mechanism remains unclear. Here we show that, in C2C12 cells, overexpression or suppression of APPL1 enhanced or suppressed, respectively, adiponectin-stimulated p38 MAPK upstream kinase cascade, consisting of transforming growth factor-β-activated kinase 1 (TAK1) and mitogen-activated protein kinase kinase 3 (MKK3). In vitro affinity binding and coimmunoprecipitation experiments revealed that TAK1 and MKK3 bind to different regions of APPL1, suggesting that APPL1 functions as a scaffolding protein to facilitate adiponectin-stimulated p38 MAPK activation. Interestingly, suppressing APPL1 had no effect on TNFα-stimulated p38 MAPK phosphorylation in C2C12 myotubes, indicating that the stimulatory effect of APPL1 on p38 MAPK activation is selective. Taken together, our study demonstrated that the TAK1-MKK3 cascade mediates adiponectin signaling and uncovers a scaffolding role of APPL1 in regulating the TAK1-MKK3-p38 MAPK pathway, specifically in response to adiponectin stimulation.

scholarly journals The Expanding Role of p38 Mitogen-Activated Protein Kinase in Programmed Host Cell Death

2019 ◽  
Vol 12 ◽  
pp. 117863611986459 ◽  
Author(s):  
Jessica Gräb ◽  
Jan Rybniker
Keyword(s):  
Protein Kinase ◽  
Host Cell ◽  
P38 Mapk ◽  
Bacterial Infections ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Host Cell Apoptosis ◽  
Mitogen Activated Protein ◽  
P38 Mapk Inhibitors ◽  
Mapk Inhibitors

The p38 mitogen-activated protein kinase (MAPK) is involved in a multitude of essential cellular processes. The kinase is activated in response to environmental stresses, including bacterial infections and inflammation, to regulate the immune response of the host. However, recent studies have demonstrated that pathogens can manipulate p38 MAPK signaling for their own benefit to either prevent or induce host cell apoptosis. In addition, there is evidence demonstrating that p38 MAPK is a potent trigger of pathogen-induced necrosis driven by mitochondrial membrane disruption. Given the large number of p38 MAPK inhibitors that have been tested in clinical trials, these findings provide an opportunity to repurpose these drugs for improved control of infectious diseases.

MAPK signaling pathways are needed for survival of H9c2 cardiac myoblasts under extracellular alkalosis

2008 ◽  
Vol 295 (3) ◽  
pp. H1319-H1329 ◽  
Author(s):  
Konstantina Stathopoulou ◽  
Isidoros Beis ◽  
Catherine Gaitanaki
Keyword(s):  
Signaling Pathways ◽  
P38 Mapk ◽  
Cardiac Myocyte ◽  
Consensus Sequence ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Dependent Manner ◽  
Selective Inhibitors ◽  
Cardiac Myoblasts ◽  
Mapk Signaling Pathways

pH is one of the most important physiological parameters, with its changes affecting the function of vital organs like the heart. However, the effects of alkalosis on the regulation of cardiac myocyte function have not been extensively investigated. Therefore, we decided to study whether the mitogen-activated protein kinase (MAPK) signaling pathways [c-Jun NH2-terminal kinases (JNKs), extracellular signal-regulated kinases (ERKs), and p38 MAPK] are activated by alkalosis induced with Tris-Tyrode buffer at two pH values, 8.5 and 9.5, in H9c2 rat cardiac myoblasts. These buffers also induced intracellular alkalinization comparable to that induced by 1 mM NH4Cl. The three MAPKs examined presented differential phosphorylation patterns that depended on the severity and the duration of the stimulus. Inhibition of Na+/H+ exchanger (NHE)1 by its inhibitor HOE-642 prevented alkalinization and partially attenuated the alkalosis (pH 8.5)-induced activation of these kinases. The same stimulus also promoted c-Jun phosphorylation and enhanced the binding at oligonucleotides bearing the activator protein-1 (AP-1) consensus sequence, all in a JNK-dependent manner. Additionally, mitogen- and stress-activated kinase 1 (MSK1) was transiently phosphorylated by alkalosis (pH 8.5), and this was abolished by the selective inhibitors of either p38 MAPK or ERK pathways. JNKs also mediated Bcl-2 phosphorylation in response to incubation with the alkaline medium (pH 8.5), while selective inhibitors of the three MAPKs diminished cell viability under these conditions. All these data suggest that alkalosis activates MAPKs in H9c2 cells and these kinases, in turn, modify proteins that regulate gene transcription and cell survival.

scholarly journals Role of Mitogen- and Stress-Activated Kinases in Ischemic Injury

2002 ◽  
Vol 22 (6) ◽  
pp. 631-647 ◽  
Author(s):  
Elaine A. Irving ◽  
Mark Bamford
Keyword(s):  
Cell Death ◽  
Cerebral Ischemia ◽  
Protein Kinase ◽  
Signaling Pathways ◽  
Focal Cerebral Ischemia ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Amino Terminal ◽  
Biological Responses ◽  
Mitogen Activated Protein

Protein kinase-mediated signaling cascades constitute the major route by which cells respond to their extracellular environment. Of these, three well-characterized mitogen-activated protein kinase (MAPK) signaling pathways are those that use the extracellular signal-regulated kinase (ERK1/2) or the stress-activated protein kinase (p38/SAPK2 or JNK/SAPK) pathways. Mitogenic stimulation of the MAPK-ERK1/2 pathway modulates the activity of many transcription factors, leading to biological responses such as proliferation and differentiation. In contrast, the p38/SAPK2 and JNK/SAPK (c-Jun amino-terminal kinase/stress-activated protein kinase) pathways are only weakly, if at all, activated by mitogens, but are strongly activated by stress stimuli. There is now a growing body of evidence showing that these kinase signaling pathways become activated following a variety of injury stimuli including focal cerebral ischemia. Whether their activation, however, is merely an epiphenomenon of the process of cell death, or is actually involved in the mechanisms underlying ischemia-induced degeneration, remains to be fully understood. This review provides an overview of the current understanding of kinase pathway activation following cerebral ischemia and discusses the evidence supporting a role for these kinases in the mechanisms underlying ischemia-induced cell death.

Divergent cell signaling after short-term intensified endurance training in human skeletal muscle

2008 ◽  
Vol 295 (6) ◽  
pp. E1427-E1438 ◽  
Author(s):  
Boubacar Benziane ◽  
Timothy J. Burton ◽  
Brendan Scanlan ◽  
Dana Galuska ◽  
Benedict J. Canny ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Kinase ◽  
Endurance Training ◽  
P38 Mapk ◽  
Acute Exercise ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Muscle Plasticity ◽  
Exercise Induced ◽  
Response To Exercise

Endurance training represents one extreme in the continuum of skeletal muscle plasticity. The molecular signals elicited in response to acute and chronic exercise and the integration of multiple intracellular pathways are incompletely understood. We determined the effect of 10 days of intensified cycle training on signal transduction in nine inactive males in response to a 1-h acute bout of cycling at the same absolute workload (164 ± 9 W). Muscle biopsies were taken at rest and immediately and 3 h after the acute exercise. The metabolic signaling pathways, including AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR), demonstrated divergent regulation by exercise after training. AMPK phosphorylation increased in response to exercise (∼16-fold; P < 0.05), which was abrogated posttraining ( P < 0.01). In contrast, mTOR phosphorylation increased in response to exercise (∼2-fold; P < 0.01), which was augmented posttraining ( P < 0.01) in the presence of increased mTOR expression ( P < 0.05). Exercise elicited divergent effects on mitogen-activated protein kinase (MAPK) pathways after training, with exercise-induced extracellular signal-regulated kinase (ERK) 1/2 phosphorylation being abolished ( P < 0.01) and p38 MAPK maintained. Finally, calmodulin kinase II (CaMKII) exercise-induced phosphorylation and activity were maintained ( P < 0.01), despite increased expression (∼2-fold; P < 0.05). In conclusion, 10 days of intensified endurance training attenuated AMPK, ERK1/2, and mTOR, but not CaMKII and p38 MAPK signaling, highlighting molecular pathways important for rapid functional adaptations and maintenance in response to intensified endurance exercise and training.

p38 Mitogen-Activated Protein Kinase and Hematologic Malignancies

2009 ◽  
Vol 133 (11) ◽  
pp. 1850-1856
Author(s):  
Yongdong Feng ◽  
Jianguo Wen ◽  
Chung-Che(Jeff) Chang
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Cell Types ◽  
Hematologic Malignancies ◽  
Mapk Signaling ◽  
Chemotherapeutic Agents ◽  
Mitogen Activated Protein Kinase ◽  
Cellular Functions ◽  
Downstream Effects ◽  
Mitogen Activated Protein

Abstract Context.—p38 mitogen-activated protein kinase (MAPK) signaling has been implicated in responses ranging from apoptosis to cell cycle, induction of expression of cytokine genes, and differentiation. This plethora of activators conveys the complexity of the p38 pathway. This complexity is further complicated by the observation that the downstream effects of p38 MAPK activation may be different depending on types of stimuli, cell types, and various p38 MAPK isoforms involved. Objective.—This review focuses on the recent advancement of the p38 MAPK isoforms as well as the roles of p38 MAPK in hematologic malignancies. Data Sources.—Review of pertinent published literature and work in our laboratory. Conclusions.—In some hematologic malignancies, activation of p38 plays a key role in promoting or inhibiting proliferation and also in increasing resistance to chemotherapeutic agents. The importance of different p38 isoforms in various cellular functions has been acknowledged recently. Further understanding of these isoforms will allow the design of more specific inhibitors to target particular isoforms to maximize the treatment effect and minimize the side effects for treating hematopoietic malignancies.

Sign in / Sign up

Export Citation Format

Share Document