Preparation of Snake Neurotoxin Nanocapsules and the Analgesic Mechanism of P38 Mitogen-Activated Protein Kinase Signal Pathway Combining Snake Neurotoxin Nanocapsules with Gabapentin

2021 ◽  
Vol 13 (3) ◽  
pp. 463-472
Author(s):  
Fengting Yin ◽  
Xiaokun Li ◽  
Weili Zhang
Keyword(s):  
Neuropathic Pain ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Glycolic Acid ◽  
Mapk Signaling ◽  
Signal Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Water Phase ◽  
Mitogen Activated Protein ◽  
Snake Neurotoxin

This study aimed to explore the analgesic effect of snake neurotoxin combined with gabapentin (Gab) on neuropathic pain in rats with chronic compression injury (CCI) of the sciatic nerve based on the nanotechnology. Firstly, various solutions were prepared to obtain the inner water phase, the oil phase, the outer water phase, and the dilution phase. Poly(lactic-co-glycolic) Acid (PLGA) and polyethylene glycol-poly(lactic-co-glycolic) acid (PEG-PLGA) were added to the prepared oil phase solution to obtain the PLGA snake neurotoxin nanocapsule and PEG-PLGA snake neurotoxin nanocapsule, respectively. After the nanocapsules were obtained, a rat CCI model was further modelled, and the reactive oxygen species (ROS) content in the rat brain tissue was analyzed and tested by the kit, and the optimal physical conditions for preparing the nanocapsules were tested. In order to test the effect of nanocapsules on the p38 mitogen-activated protein kinase (MAPK) signaling pathway, the rats were divided into Control group, Sham group, CCI group, Gabapentin (Gab) group, and PEG-PLGA snake neurotoxin nanocapsule + Gab group. The rats in different groups were given abdominal injections to compare relevant indicators of signal pathway. In the experiment, neuropathic pain was related to changes in ROS content, and snake neurotoxin nanocapsules could reduce the ROS content; PLGA snake neurotoxin nanocapsules and PEG-PLGA snake neurotoxin nanocapsules had encapsulation efficiencys of 24.7% and 22.8% and drug loading of 3.28% and 3.02%, respectively, and the particle sizes of prepared nanocapsules were 760 nm~1,150 nm. Besides, the phase transition temperature of about 50 °C and the light time of 1 h can accelerate the release of nanocapsules to the greatest extent; and the snake neurotoxin could inhibit the activation of p38 MAPK signaling pathway so as to play the analgesic effects on neuropathic pain.

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 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 Linc02381 Exacerbates Rheumatoid Arthritis Through Adsorbing miR-590-5p and Activating the Mitogen-Activated Protein Kinase Signaling Pathway in Rheumatoid arthritis-fibroblast-like synoviocytes

2020 ◽  
Vol 29 ◽  
pp. 096368972093802
Author(s):  
Jing Wang ◽  
Qing Zhao
Keyword(s):  
Rheumatoid Arthritis ◽  
Cell Proliferation ◽  
Protein Kinase ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein ◽  
Synovial Tissues ◽  
Proliferation And Invasion ◽  
Fibroblast Like Synoviocytes

Rheumatoid arthritis (RA) is a chronic systemic autoimmune disease. New evidence suggested that linc02381 suppressed colorectal cancer progression by regulating PI3 K signaling pathway, but the role of linc02381 in other diseases, such as RA, remains unclear. This study aimed to reveal the mechanism of linc02381 in RA progression. In vivo and in vitro, we found that linc02381 was upregulated in RA synovial tissues or RA fibroblast-like synoviocytes (RA-FLSs, P < 0.01), which were detected by quantitative real-time polymerase chain reaction. Cell Counting Kit-8, EDU, and Transwell assays revealed that linc02381 overexpression enhanced cell proliferation and invasion, and linc02381 knockdown inhibited cell proliferation and invasion in FLSs. Moreover, the results of bioinformatics analysis, luciferase reporter gene assay, and pull-down assay verified that linc02381 could directly bind with miR-590-5p. MiR-590-5p was downregulated in RA-FLSs, and overexpression of linc02381 suppressed expression of miR-590-5p that post-transcriptionally suppressed the expression of mitogen-activated protein kinase kinase 3 (MAP2K3), and overexpression of miR-590-5p reversed the effect of linc02381 overexpression on MAP2K3 expression. MiR-590-5p inhibitor reversed the inhibition effect of linc02381 knockdown on proliferation and invasion of FLSs, which enhanced expression of MAP2K3, and activation of p38 and AP-1 in the MAPK signaling pathway. In summary, linc02381 was upregulated in RA synovial tissues and RA-FLSs, and it exacerbated RA by adsorbing miR-590-5p to activate the MAPK signaling pathway.

scholarly journals Adenosine Triphosphate Activates Mitogen-Activated Protein Kinase in Human Granulosa-Luteal Cells*

Endocrinology ◽  
2001 ◽  
Vol 142 (4) ◽  
pp. 1554-1560 ◽  
Author(s):  
Chen-Jei Tai ◽  
Sung Keun Kang ◽  
Chii-Ruey Tzeng ◽  
Peter C. K. Leung
Keyword(s):  
Protein Kinase ◽  
Signaling Pathway ◽  
Mapk Signaling ◽  
Mapk Signaling Pathway ◽  
Mitogen Activated Protein Kinase ◽  
Intracellular Camp ◽  
Human Ovary ◽  
Luteal Cells ◽  
Mitogen Activated Protein

Abstract ATP has been shown to activate the phospholipase C/diacylglycerol/protein kinase C (PKC) pathway. However, little is known about the downstream signaling events. The present study was designed to examine the effect of ATP on activation of the mitogen-activated protein kinase (MAPK) signaling pathway and its physiological role in human granulosa-luteal cells. Western blot analysis, using a monoclonal antibody that detected the phosphorylated forms of extracellular signal-regulated kinase-1 and -2 (p42mapk and p44 mapk, respectively), demonstrated that ATP activated MAPK in a dose- and time-dependent manner. Treatment of the cells with suramin (a P2 purinoceptor antagonist), neomycin (a phospholipase C inhibitor), staurosporin (a PKC inhibitor), or PD98059 (an MAPK/ERK kinase inhibitor) significantly attenuated the ATP-induced activation of MAPK. In contrast, ATP-induced MAPK activation was not significantly affected by pertussis toxin (a Gi inhibitor). To examine the role of Gs protein, the intracellular cAMP level was determined after treatment with ATP or hCG. No significant elevation of intracellular cAMP was noted after ATP treatment. To determine the role of MAPK in steroidogenesis, human granulosa-luteal cells were treated with ATP, hCG, or ATP plus hCG in the presence or absence of PD98059. RIA revealed that ATP alone did not significantly affect the basal progesterone concentration. However, hCG-induced progesterone production was reduced by ATP treatment. PD98059 reversed the inhibitory effect of ATP on hCG-induced progesterone production. To our knowledge, this is the first demonstration of ATP-induced activation of the MAPK signaling pathway in the human ovary. These results support the idea that the MAPK signaling pathway is involved in mediating ATP actions in the human ovary.

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