scholarly journals Contribution of p38 MAPK to the Ameliorating Effect of Enriched Environment on the Cognitive Deficits Induced by Chronic Cerebral Hypoperfusion

2016 ◽  
Vol 40 (3-4) ◽  
pp. 549-557 ◽  
Author(s):  
Yu-Wang Li ◽  
Qing-Yun Li ◽  
Jin-Hua Wang ◽  
Xiao-Lin Xu
Keyword(s):  
P38 Mapk ◽  
Cognitive Deficits ◽  
Mapk Signaling ◽  
Selective Inhibitor ◽  
Enriched Environment ◽  
Chronic Cerebral Hypoperfusion ◽  
Mitogen Activated Protein Kinase ◽  
Cerebral Hypoperfusion ◽  
Memory Impairments ◽  
Mitogen Activated Protein

Background/Aims: An enriched environment (EE) ameliorates learning and memory impairments induced by chronic cerebral hypoperfusion, and the p38 mitogen-activated protein kinase (p38 MAPK) signaling pathway exerts both beneficial and deleterious effects on the nervous system during the progression of ischemia. Methods: The present study investigated whether p38 MAPK participates in the process by which EE exposure ameliorates the cognitive deficits induced by chronic cerebral hypoperfusion. Results: EE exposure significantly enhanced the cognitive performance of vascular dementia (VD) model rats, and p38 MAPK protein decreased in parallel with cognitive improvements. Inhibition of p38 MAPK function by its selective inhibitor SB203580 improved the cognition index of VD rats and upregulated p38 MAPK expression with p38 MAPK antisense oligodeoxynucleotides. This impaired cognition in VD rats could not be rescued by EE exposure. Conclusion: p38 MAPK participates in the process by which EE exposure ameliorates cognitive deficits induced by chronic cerebral hypoperfusion.

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.

p38 MAPK Signaling Mediates Retinoic Acid-Induced Expression of a Novel Tumor Suppressor Protein Programmed Cell Death 4 (PDCD4) in Acute Promyelocytic Leukemia Cells.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1942-1942
Author(s):  
Ugur Akar ◽  
Bulent Ozpolat ◽  
Nancy Colburn ◽  
Gabriel Lopez-Berestein
Keyword(s):  
Retinoic Acid ◽  
Cell Differentiation ◽  
P38 Mapk ◽  
Myeloid Cell ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Granulocytic Differentiation ◽  
P38 Inhibitor ◽  
Pdcd4 Expression ◽  
Mitogen Activated Protein

Abstract Programmed-cell-death-4 (PDCD4) is a novel tumor suppressor protein that suppresses tumor promoter-induced neoplastic transformation. PDCD4 specifically inhibits the helicase activity of eukaryotic translation initiation factor 4A (eIF4A) and translation initiation and cap-dependent mRNA translation in vitro and in vivo. Loss or underexpression of PDCD4 is associated with carcinogenesis and chemoresistance in solid tumors. The role and regulation of PDCD4 in the the hematopoietic system and myeloid leukemia cells are not known. We previously reported that ATRA induces translational suppression through multiple posttranscriptional mechanisms during terminal cell differentiation (Harris et al, Blood, 104 (5) 2004). Therefore, in this study, we investigated the expression and regulation of PDCD4 during myeloid cell differentiation. All-trans-retinoic acid (ATRA) induces terminal differentiation in acute myeloid leukemia (AML) and promyelocytic (APL) cells, a well established model for myeloid cell differentiation. We found that treatment of HL60 (M2 type AML) and NB4 APL (M3 type AML) cells with ATRA (1 mM) induced PDCD4 protein and mRNA expression during granulocytic differentiation detected by western blot and RT-PCR analysis, respectively. We also demonstrated that inhibition of PDCD4 by siRNA reduced granulocytic differentiation induced by ATRA, suggesting that PDCD4 plays a role in granuliocytic differentiation. To determine mechanisms regulating PDCD4 we investigated the role of pP38 MAPK (Mitogen activated protein kinase) in reugulation of PDCD4 expression. ATRA induced PDCD4 expression correlated with activation of p38 MAPK (Mitogen Activated Protein Kinase) pathway in NB4 cells. To test the hypothesis that p38 MAPK signaling pathway mediates retinoic acid induced PDCD4 expression we treated cells with a specific p38 MAPK inhibitor, SB203580, ATRA or combination with ATRA. We observed that p38 inhibitor inhibited ATRA-induced expression of PDCD4 in NB4 cells. Basal level of PDCD4 expression was also markedly downregulated in the presence of p38 inhibitor when compared to untreated control cells, suggesting that p38 pathway is involved in ATRA-dependent and independent PDCD4 expression. Currently we are investigating whether inhibition of p38 by small interfering RNA (siRNA) will prevent expression of ATRA induced PDCD4 in APL cells. We are also trying to identify whether ATF2 transcription factor, a downstream of p38, is involved in PDCD4 expression. p38-mediated induction of PDCD4 pathway reveals a novel mechanism of PDCD4 regulation and ATRA action, providing a new insight into understanding terminal differentiation of myeloid cells. Better understanding the role of PDCD4 and posttranscriptional control of gene expression may offer targets for the differentiation therapy and chemo preventive strategies.

Expression of p38 MAPK in Acute Lung Injury Induced by LPS in Mice

2014 ◽  
Vol 522-524 ◽  
pp. 332-336 ◽  
Author(s):  
Kai Xiu Qin ◽  
Yong Wang ◽  
Hua Gang Jian
Keyword(s):  
Endothelial Cells ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
P38 Mapk ◽  
Inflammatory Cells ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Control Group ◽  
Mitogen Activated Protein ◽  
Set Up

Objective To investigate the expression and roles of p38 mitogen-activated protein kinase (p38 MAPK) in LPS-induced acute lung injury (ALI) in mice. Methods The ALI mice models were set up by intraperineal injection of lipopolysaccharide (LPS). The expressions of p38 MAPK in lung tissues were detected by immunohistochemistry and Western-blot. Results The positive expressions of p38 MAPK distribute mainly in infiltrative inflammatory cells, epithelial cells and endothelial cells. And the level of expression of phosphated p38 MAPK in ALI group were higher obviously than that in the control group, and it reached a peak after two hours. Conclusion p38 MAPK signaling pathway was triggered by ALI induced by endotoxin.

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.

scholarly journals Store-operated Ca2+ Entry (SOCE) Induced by Protease-activated Receptor-1 Mediates STIM1 Protein Phosphorylation to Inhibit SOCE in Endothelial Cells through AMP-activated Protein Kinase and p38β Mitogen-activated Protein Kinase

2013 ◽  
Vol 288 (23) ◽  
pp. 17030-17041 ◽  
Author(s):  
Premanand C. Sundivakkam ◽  
Viswanathan Natarajan ◽  
Asrar B. Malik ◽  
Chinnaswamy Tiruppathi
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
P38 Mapk ◽  
Transient Receptor Potential ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mouse Lung ◽  
Mitogen Activated Protein ◽  
Protease Activated Receptor 1 ◽  
Amp Activated Protein Kinase

The Ca2+ sensor STIM1 is crucial for activation of store-operated Ca2+ entry (SOCE) through transient receptor potential canonical and Orai channels. STIM1 phosphorylation serves as an “off switch” for SOCE. However, the signaling pathway for STIM1 phosphorylation is unknown. Here, we show that SOCE activates AMP-activated protein kinase (AMPK); its effector p38β mitogen-activated protein kinase (p38β MAPK) phosphorylates STIM1, thus inhibiting SOCE in human lung microvascular endothelial cells. Activation of AMPK using 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR) resulted in STIM1 phosphorylation on serine residues and prevented protease-activated receptor-1 (PAR-1)-induced Ca2+ entry. Furthermore, AICAR pretreatment blocked PAR-1-induced increase in the permeability of mouse lung microvessels. Activation of SOCE with thrombin caused phosphorylation of isoform α1 but not α2 of the AMPK catalytic subunit. Moreover, knockdown of AMPKα1 augmented SOCE induced by thrombin. Interestingly, SB203580, a selective inhibitor of p38 MAPK, blocked STIM1 phosphorylation and led to sustained STIM1-puncta formation and Ca2+ entry. Of the three p38 MAPK isoforms expressed in endothelial cells, p38β knockdown prevented PAR-1-mediated STIM1 phosphorylation and potentiated SOCE. In addition, inhibition of the SOCE downstream target CaM kinase kinase β (CaMKKβ) or knockdown of AMPKα1 suppressed PAR-1-mediated phosphorylation of p38β and hence STIM1. Thus, our findings demonstrate that SOCE activates CaMKKβ-AMPKα1-p38β MAPK signaling to phosphorylate STIM1, thereby suppressing endothelial SOCE and permeability responses.

scholarly journals Effects of ethanol on mitogen-activated protein kinase and stress-activated protein kinase cascades in normal and regenerating liver

1998 ◽  
Vol 334 (3) ◽  
pp. 669-676 ◽  
Author(s):  
Jianping CHEN ◽  
Edward J. N. ISHAC ◽  
Paul DENT ◽  
George KUNOS ◽  
Bin GAO
Keyword(s):  
Protein Kinase ◽  
P38 Mapk ◽  
Ethanol Exposure ◽  
Selective Inhibitor ◽  
Chronic Ethanol ◽  
Mitogen Activated Protein Kinase ◽  
Hepatocyte Proliferation ◽  
Mapk Activation ◽  
Chronic Ethanol Consumption ◽  
Mitogen Activated Protein

To understand the mechanisms by which ethanol inhibits hepatocyte proliferation, we studied the effects of ethanol on p42/44 mitogen-activated protein kinase (MAPK), p38 mitogen-activated protein kinase (p38 MAPK) and c-Jun N-terminal kinase (JNK) in normal and regenerating rat liver. Treatment of rat hepatocytes with 100 mM ethanol in vitro for 16 h prolonged the activation of p42/44 MAPK and p38 MAPK induced by various agonists. Such treatment also increased basal JNK activity, but did not potentiate or prolong agonist-induced JNK activation. Ethanol potentiation of the activation of p42/44 MAPK was abolished by pertussis toxin. In contrast, chronic ethanol consumption in vivo inhibited the activation of p42/44 MAPK, p38 MAPK and JNK induced either by partial hepatectomy or by various agonists. However, both acute and chronic ethanol inhibited hepatocyte proliferation induced by insulin and epidermal growth factor. A selective inhibitor of p42/44 MAPK partially prevented the inhibition of hepatocyte proliferation caused by acute, but not by chronic, ethanol exposure, whereas a selective inhibitor of p38 MAPK further inhibited hepatocyte proliferation under both conditions. These data suggest that acute and chronic ethanol inhibit hepatocyte proliferation by different mechanisms. The effect of acute ethanol may be related to the prolongation of p42/44 MAPK activation, whereas inhibition of hepatocyte proliferation by chronic ethanol may be due to inhibition of p38 MAPK activation.

scholarly journals cGMP-dependent Protein Kinase Type I Inhibits TAB1-p38 Mitogen-activated Protein Kinase Apoptosis Signaling in Cardiac Myocytes

2006 ◽  
Vol 281 (43) ◽  
pp. 32831-32840 ◽  
Author(s):  
Beate Fiedler ◽  
Robert Feil ◽  
Franz Hofmann ◽  
Christian Willenbockel ◽  
Helmut Drexler ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Cardiac Myocytes ◽  
P38 Mapk ◽  
Cardiac Myocyte ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Type I ◽  
Mapk Phosphorylation ◽  
Mitogen Activated Protein ◽  
Dependent Protein

Cardiac myocyte apoptosis during ischemia and reperfusion (I/R) is tightly controlled by a complex network of stress-responsive signaling pathways. One pro-apoptotic pathway involves the interaction of the scaffold protein TAB1 with p38 mitogen-activated protein kinase (p38 MAPK) leading to the autophosphorylation and activation of p38 MAPK. Conversely, NO and its second messenger cGMP protect cardiac myocytes from apoptosis during I/R. We provide evidence that the cGMP target cGMP-dependent protein kinase type I (PKG I) interferes with TAB1-p38 MAPK signaling to protect cardiac myocytes from I/R injury. In isolated neonatal cardiac myocytes, activation of PKG I inhibited the interaction of TAB1 with p38 MAPK, p38 MAPK phosphorylation, and apoptosis induced by simulated I/R. During I/R in vivo, mice with a cardiac myocyte-restricted deletion of PKG I displayed a more pronounced interaction of TAB1 with p38 MAPK and a stronger phosphorylation of p38 MAPK in the myocardial area at risk during reperfusion and more apoptotic cardiac myocytes in the infarct border zone as compared with wild-type littermates. Notably, adenoviral expression of a constitutively active PKG I mutant truncated at the N terminus(PKGI-ΔN1-92) did not inhibit p38 MAPK phosphorylation and apoptosis induced by simulated I/R in vitro, indicating that the N terminus of PKG I is required. As shown by co-immunoprecipitation experiments in HEK293 cells, cGMP-activated PKG I, but not constitutively active PKG I-ΔN1-92 or PKG I mutants carrying point mutations in the N-terminal leucine-isoleucine zipper, interacted with p38 MAPK, and prevented the binding of TAB1 to p38 MAPK. Together, our data identify a novel interaction between the cGMP target PKG I and the TAB1-p38 MAPK signaling pathway that serves as a defense mechanism against myocardial I/R injury.

scholarly journals Hp-s1 Ganglioside Suppresses Proinflammatory Responses by Inhibiting MyD88-Dependent NF-κB and JNK/p38 MAPK Pathways in Lipopolysaccharide-Stimulated Microglial Cells

Marine Drugs ◽  
2020 ◽  
Vol 18 (10) ◽  
pp. 496
Author(s):  
Jui-Hu Shih ◽  
Yow-Fu Tsai ◽  
I-Hsun Li ◽  
Ming-Hua Chen ◽  
Yuahn-Sieh Huang
Keyword(s):  
P38 Mapk ◽  
Underlying Mechanism ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Microglial Cells ◽  
Cell Counting ◽  
Mitogen Activated Protein ◽  
Proinflammatory Responses ◽  
A Cell ◽  
Myeloid Differentiation Factor

Hp-s1 ganglioside is isolated from the sperm of sea urchin (Hemicentrotus pulcherrimus). In addition to neuritogenic activity, the biological function of Hp-s1 in neuroinflammation is unknown. In this study, we investigated the anti-neuroinflammatory effect of Hp-s1 on lipopolysaccharide (LPS)-stimulated microglial cells. MG6 microglial cells were stimulated with LPS in the presence or absence of different Hp-s1 concentrations. The anti-inflammatory effect and underlying mechanism of Hp-s1 in LPS-activated microglia cells were assessed through a Cell Counting kit-8 assay, Western blot analysis, and immunofluorescence. We found that Hp-s1 suppressed not only the expression of inducible nitric oxide synthase and cyclooxygenase-2 but also the expression of proinflammatory cytokines, such as TNF-α, IL-1β, and IL-6. Hp-s1 inhibited the LPS-induced NF-κB signaling pathway by attenuating the phosphorylation and translocation of NF-κB p65 and by disrupting the degradation and phosphorylation of inhibitor κB-α (IκBα). Moreover, Hp-s1 inhibited the LPS-induced phosphorylation of p38 mitogen-activated protein kinase (MAPK) and c-Jun N-terminal kinase (JNK). Hp-s1 also reduced the expression of myeloid differentiation factor 88 (MyD88) and TNF receptor-associated factors 6 (TRAF6), which are prerequisites for NF-κB and MAPKs activation. These findings indicated that Hp-s1 alleviated LPS-induced proinflammatory responses in microglial cells by downregulating MyD88-mediated NF-κB and JNK/p38 MAPK signaling pathways, suggesting further evaluation as a new anti-neuroinflammatory drug.

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