scholarly journals Antiprolactinoma Effect of Hordenine by Inhibiting MAPK Signaling Pathway Activation in Rats

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Xiong Wang ◽  
Run-zhu Guo ◽  
Li Ma ◽  
Qiao-yan Ding ◽  
Jun-hua Meng ◽  
...  
Keyword(s):  
Pituitary Gland ◽  
Signaling Pathway ◽  
Mapk Pathway ◽  
Interleukin 1 ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Pathway Activation ◽  
Mitogen Activated Protein ◽  
Jnk Activation

Prolactinomas are harmful to human health, and the clinical first-line treatment drug is bromocriptine. However, 20% prolactinomas patients did not respond to bromocriptine. Hordenine is an alkaloid separated from Fructus Hordei Germinatus, which showed significant antihyperprolactinemia activity in rats. The aim of this study was to explore the effect and mechanism of hordenine on prolactinomas in rats. The study used estradiol to induce prolactinomas, which caused the activation of the pituitary mitogen-activated protein kinase (MAPK) pathway in rats significantly. The treatment of hordenine restored estradiol, induced the overgrowth of pituitary gland, and reduced the prolactin (PRL) accumulation in the serum and pituitary gland of rats by blocking the MAPK (p38, ERK1/2, and JNK) activation and production of inflammatory cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6). The antiprolactinoma effect of hordenine was mediated by inhibiting the MAPK signaling pathway activation in rats.

The p38 mitogen-activated protein kinase pathway plays a critical role in thrombin-induced endothelial chemokine production and leukocyte recruitment

Blood ◽  
2001 ◽  
Vol 98 (3) ◽  
pp. 667-673 ◽  
Author(s):  
Valérie Marin ◽  
Catherine Farnarier ◽  
Sandra Grès ◽  
Solange Kaplanski ◽  
Michael S.-S. Su ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
P38 Mapk ◽  
Mapk Pathway ◽  
Endothelial Activation ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Chemokine Production ◽  
Mitogen Activated Protein

Abstract Thrombin, the terminal serine protease in the coagulation cascade, is a proinflammatory molecule in vivo and induces endothelial activation in vitro. The cellular signaling mechanisms involved in this function are unknown. The role of the p38 mitogen-activated protein kinase (MAPK) signaling pathway in thrombin-induced chemokine production was studied. Phosphorylation of both p38 MAPK and its substrate, ATF-2, was observed in human umbilical vein endothelial cells (HUVECs) stimulated with thrombin, with a maximum after 5 minutes of stimulation. Using the selective p38 MAPK inhibitor SB203580, there was a significant decrease in thrombin-induced interleukin-8 (IL-8) and monocyte chemotactic protein-1 (MCP-1) protein production and messenger RNA steady-state levels. In addition, SB203580 decreased IL-8 and MCP-1 production induced by the thrombin receptor-1 agonist peptide (TRAP), suggesting functional links between the thrombin G protein–coupled receptor and the p38 MAPK pathway. Furthermore, endothelial activation in the presence of SB203580 decreased the chemotactic activity of thrombin-stimulated HUVEC supernatant on neutrophils and monocytic cells. In contrast, the p42/p44 MAPK pathway did not appear to be involved in thrombin- or TRAP-induced endothelial chemokine production, because there was no reduction in the presence of the p42/p44-specific inhibitor PD98059. These results demonstrate that the p38 rather than p42/44 MAPK signaling pathway plays an important role in thrombin-induced endothelial proinflammatory activation and suggest that inhibition of p38 MAPK may be an interesting target for anti-inflammatory strategies in vascular diseases combining thrombosis and inflammation.

Inhibition of miR-200c Expression Promotes Activation of Extracellular Signal-Regulated Kinase (ERK)/ Mitogen-Activated Protein Kinase (MAPK) Signaling Pathway and Inhibits Osteogenic Differentiation in Osteoporosis Mice

2020 ◽  
Vol 10 (2) ◽  
pp. 163-168
Author(s):  
Sheng Wang ◽  
Zhonghan Min ◽  
Run Gu ◽  
Zhongwei Yu ◽  
Pingquan Chen ◽  
...  
Keyword(s):  
Osteogenic Differentiation ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Bone Diseases ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Erk Mapk ◽  
Mitogen Activated Protein ◽  
Marrow Mesenchymal Stem Cells ◽  
Sirna Group

During OP bone metabolism, activated MAPK signaling can promote the proliferation and differentiation of osteoclasts. miRNAs involve in bone diseases. Our study aimed to evaluate miR-200c’s effect on ERK/MAPK signaling pathway in OP. miR-200c expression in OP mice and normal mice was detected by qPCR. BMSCs were cultured and transfected with siRNA to establish a miR-200c knockout model. Flow cytometry was used to detect cell apoptosis and ERK/MAPK signaling protein was detected by Western blot. miR-200c expression in OP mice was significantly lower than that in normal mice. Bone marrow mesenchymal stem cells (BMSCs) contain a large amount of siRNA particles under a fluorescence microscope. siRNA transfection can effectively inhibit miR-200c expression without difference of BMSCs apoptosis between miR-200c siRNA group and NC group. However, ERK1/2 and P38 expression in experimental group were significantly higher than those in NC siRNA group with reduced ALP activity. In addition, BMSCs osteogenic differentiation was further diminished when miR-200c expression was inhibited. miR-200c expression is lower in OP mice. miR-200c siRNA inhibits BMSCs osteogenic differentiation via ERK/MAPK signaling, thereby promoting OP progression.

scholarly journals Identification of RAS-Mitogen-Activated Protein Kinase Signaling Pathway Modulators in an ERF1 Redistribution® Screen

2006 ◽  
Vol 11 (4) ◽  
pp. 423-434 ◽  
Author(s):  
Charlotta Grånäs ◽  
Betina Kerstin Lundholt ◽  
Frosty Loechel ◽  
Hans-Christian Pedersen ◽  
Sara Petersen Bjørn ◽  
...  
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Kinase Inhibitors ◽  
Mapk Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
A Cell ◽  
Protein Kinase Signaling

The RAS-mitogen-activated protein kinase (MAPK) signaling pathway has a central role in regulating the proliferation and survival of both normal and tumor cells. This pathway has been 1 focus area for the development of anticancer drugs, resulting in several compounds, primarily kinase inhibitors, in clinical testing. The authors have undertaken a cell-based, high-throughput screen using a novel ERF1 Redistribution® assay to identify compounds that modulate the signaling pathway. The hit compounds were subsequently tested for activity in a functional cell proliferation assay designed to selectively detect compounds inhibiting the proliferation of MAPK pathway-dependent cancer cells. The authors report the identification of 2 cell membrane-permeable compounds that exhibit activity in the ERF1 Redistribution® assay and selectively inhibit proliferation of MAPK pathway-dependent malignant melanoma cells at similar potencies (IC50 =< 5 μM). These compounds have drug-like structures and are negative in RAF, MEK, and ERK in vitro kinase assays. Drugs belonging to these compound classes may prove useful for treating cancers caused by excessive MAPK pathway signaling. The results also show that cell-based, high-content Redistribution® screens can detect compounds with different modes of action and reveal novel targets in a pathway known to be disease relevant.

scholarly journals Cardiovascular protective effects of GLP-1:A focus on the MAPK signaling pathway

2021 ◽  
Author(s):  
Yu-Yan Zhao ◽  
Lin-Hui Chen ◽  
Liang Huang ◽  
Yong-Zhen Li ◽  
Chen Yang ◽  
...  
Keyword(s):  
Signaling Pathway ◽  
Metabolic Diseases ◽  
Mapk Pathway ◽  
Signal Transduction Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Protective Effects ◽  
Glucagon Like Peptide 1 ◽  
Common Signal

Cardiovascular and related metabolic diseases are significant global health challenges. Glucagon-like peptide 1 (GLP-1) is a brain-gut peptide secreted by ileal endocrine that is now an established drug target in type 2 diabetes (T2DM). GLP-1 targeting agents have been shown not only to treat T2DM, but also to exert cardiovascular protective effects through regulating multiple signaling pathways. The mitogen-activated protein kinase (MAPK) pathway, a common signal transduction pathway for transmitting extracellular signals to downstream effector molecules, is involved in regulating diverse cell physiological processes, including cell proliferation, differentiation, stress, inflammation, functional synchronization, transformation and apoptosis. The purpose of this review is to highlight the relationship between GLP-1 and cardiovascular disease (CVD), and discuss how GLP-1 exerts cardiovascular protective effects through MAPK signaling pathway. This review also discusses the future challenges in fully characterizing and evaluating the CVD protective effects of GLP-1 receptor agonists (GLP-1RA) at the cellular and molecular level. A better understanding of MAPK signaling pathway that are disregulated in CVD may aid in the design and development of promising GLP-1RA.

scholarly journals Chicken avian β-defensin 8 modulates immune response via the mitogen-activated protein kinase signaling pathways in a chicken macrophage cell line

2019 ◽  
Author(s):  
Yeojin Hong ◽  
Thu Thao Pham ◽  
Jiae Lee ◽  
Hyun S. Lillehoj ◽  
Yeong Ho Hong
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Proinflammatory Cytokines ◽  
Interferon Γ ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Macrophage Cell ◽  
Mitogen Activated Protein ◽  
Chicken Macrophage

Abstract Background Defensins are antimicrobial peptides composed of three conserved disulfide bridges, a β-sheet, and both hydrophobic and cationic amino acids. In this study, we aimed to demonstrate the immunomodulation role of avian β-defensin 8 (AvBD8) in a chicken macrophage cell line.Results Chicken AvBD8 stimulated the expression of proinflammatory cytokines (interleukin (IL)-1β, interferon-γ, and IL-12p40) and chemokines (CCL4, CXCL13, and CCL20) in macrophages. Furthermore, by western blotting and immunocytochemistry, we confirmed that AvBD8 activated the mitogen-activated protein kinase (MAPK) signaling pathway via extracellular regulated kinases 1/2 (ERK1/2) and p38 signaling molecules.Conclusion Overall, AvBD8 plays a crucial role in host defense as not only an antimicrobial peptide, but also an immunomodulator by activating the MAPK signaling pathway and inducing the expression of proinflammatory cytokines and chemokines.

scholarly journals IL-6 Promotes the Proliferation and Immunosuppressive Function of Myeloid-Derived Suppressor Cells via the MAPK Signaling Pathway in Bladder Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Zhong Zheng ◽  
Xinyi Zheng ◽  
Yiwen Zhu ◽  
Zhixian Yao ◽  
Weiguang Zhao ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Signaling Pathway ◽  
Suppressor Cells ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Myeloid Derived Suppressor Cells ◽  
Mitogen Activated Protein ◽  
Proliferation Ability ◽  
Muscle Invasive

Muscle-invasive bladder cancer (MIBC) is characterized by a highly complex immune environment, which is not well understood. Interleukin-6 (IL-6) is generated and secreted by multifarious types of cells, including tumor cells. This study was aimed at demonstrating that the levels of IL-6 and the number of myeloid-derived suppressor cells (MDSCs), with a positive correlation between them, increased in MIBC tissues, promoting MIBC cell proliferation, especially in patients with recurrence. In coculture analysis, MDSCs, with the stimulation of IL-6, could significantly lower the proliferation ability of CD4+ or CD8+ T lymphocytes. Further, this study demonstrated that IL-6 could upregulate the mitogen-activated protein kinase (MAPK) signaling pathway in MDSCs. The MAPK signaling inhibitor, aloesin, partially reversed the effects of IL-6 on MDSCs. These data suggested that IL-6 promoted MIBC progression by not only accelerating proliferation but also improving the immune suppression ability of MDSCs through activating the MAPK signaling pathway.

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