scholarly journals Extracellular Signal-Regulated Kinase 5 in the Cerebrospinal Fluid-Contacting Nucleus Contributes to Neuropathic Pain in Rats

2015 ◽  
Vol 6;18 (6;11) ◽  
pp. E1073-E1082
Author(s):  
Li-Cai Zhang
Keyword(s):  
Neuropathic Pain ◽  
Mechanical Allodynia ◽  
Chronic Constriction Injury ◽  
Camp Response Element Binding ◽  
Camp Response Element ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Element Binding Protein ◽  
Thermal Hypersensitivity

Background: The activation of mitogen-activated protein kinases (MAPKs) have been observed in synaptic plasticity processes of learning and memory in neuropathic pain. Cerebrospinal fluidcontacting nucleus (CSF-CN) has been identified with the onset and persistence of neuropathic pain. However, whether extracellular signal-regulated protein kinase 5 (ERK5), a member of MAPKs, in CSF-CN participates in neuropathic pain has not been studied yet. Objective: The aim of the present study was to identify the role of ERK5 in CSF-CN on the formation and development of neuropathic pain, and to investigate its possible mechanism. Study Design: Controlled animal study. Setting: University laboratory. Methods: After a chronic constriction injury (CCI) model was produced, BIX02188 was dissolved in 1% DMSO and injected into the lateral ventricles LV in a volume of 3 μl with different doses (0.1 μg, 1 μg, 10 μg). Mechanical allodynia and thermal hypersensitivity behavioral test, immunofluorescence, and western blot technique were used in this research. Result: Following CCI, mechanical allodynia and thermal hypersensitivity were developed within a day, peaked at 14 days, and persisted for 21 days. ERK5 was remarkably activated by CCI in CSFCN. Moreover, selective inhibiting of p-ERK5 expression in CSF-CN by BIX02188 could significantly relieve CCI-induced mechanical allodynia and thermal hypersensitivity, accompanying with the decreased phosphorylation of cAMP response-element binding protein (CREB) in CSF-CN. Limitations: More underlying mechanism(s) of the role of ERK5 in CSF-CN on the formation and development of neuropathic pain will be needed to explore in future research. Conclusion: These findings suggest activation of ERK5 in CSF-CN might contribute to the onset and development of neuropathic pain and its role might be partly accomplished by p-CREB. Key words: Neuropathic pain, extracellular signal-regulated kinase 5, distal cerebrospinal fluidcontacting neurons, cerebrospinal fluid-contacting nucleus, chronic constriction injury, cAMP response-element binding protein

scholarly journals Stimulation of Phosphorylation of ERK and CREB by Phellopterin and Auraptene Isolated from Citrus junos

2014 ◽  
Vol 9 (10) ◽  
pp. 1934578X1400901 ◽  
Author(s):  
Mitsuhiro Nakamura ◽  
Tomoko Suzuki ◽  
Mai Takagi ◽  
Hirotoshi Tamura ◽  
Toshiya Masuda
Keyword(s):  
Camp Response Element Binding ◽  
Long Term Memory ◽  
Camp Response Element ◽  
Extracellular Signal Regulated Kinase ◽  
Cellular Processes ◽  
Extracellular Signal ◽  
Citrus Junos ◽  
Element Binding Protein ◽  
Methyl Ferulate

Bioactive compounds from citrus fruits contribute many benefits to human health. Extracellular signal-regulated kinase (ERK) signaling plays an important role in the regulation of multiple cellular processes. Activation of the ERK-cAMP response element binding protein (CREB) signaling is required for long-term memory formation. In this study, auraptene, phellopterin, thymol, coniferyl alcohol 9-methyl ether and methyl ferulate were isolated from Citrus junos. Among the five compounds isolated, auraptene and phellopterin increased the phosphorylation of ERK and CREB. This study provides, to our knowledge, the first evidence that phellopterin potently stimulates the phosphorylation of ERK and CREB. Phellopterin could be a novel neuroprotective agent.

scholarly journals p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) modulates co-operation between myocyte enhancer factor 2A (MEF2A) and thyroid hormone receptor-retinoid X receptor

2003 ◽  
Vol 369 (3) ◽  
pp. 477-484 ◽  
Author(s):  
Antonio De LUCA ◽  
Anna SEVERINO ◽  
Paola De PAOLIS ◽  
Giuliano COTTONE ◽  
Luca De LUCA ◽  
...  
Keyword(s):  
Thyroid Hormone ◽  
Binding Protein ◽  
Camp Response Element Binding ◽  
Creb Binding Protein ◽  
Camp Response Element ◽  
Response Element ◽  
Adenovirus E1a ◽  
Element Binding Protein ◽  
Enhancer Factor

Thyroid hormone receptors (TRs) and members of the myocyte enhancer factor 2 (MEF2) family are involved in the regulation of muscle-specific gene expression during myogenesis. Physical interaction between these two factors is required to synergistically activate gene transcription. p300/cAMP-response-element-binding-protein ('CREB')-binding protein (CBP) interacting with transcription factors is able to increase their activity on target gene promoters. We investigated the role of p300 in regulating the TR—MEF2A complex. To this end, we mapped the regions of these proteins involved in physical interactions and we evaluated the expression of a chloramphenicol acetyltransferase (CAT) reporter gene in U2OS cells under control of the α-myosin heavy chain promoter containing the thyroid hormone response element (TRE). Our results suggested a role of p300/CBP in mediating the transactivation effects of the TR—retenoid X receptor (RxR)—MEF2A complex. Our findings showed that the same C-terminal portion of p300 binds the N-terminal domains of both TR and MEF2A, and our in vivo studies demonstrated that TR, MEF2A and p300 form a ternary complex. Moreover, by the use of CAT assays, we demonstrated that adenovirus E1A inhibits activation of transcription by TR—RxR—MEF2A—p300 but not by TR—RxR—MEF2A. Our data suggested that p300 can bind and modulate the activity of TR—RxR—MEF2A at TRE. In addition, it is speculated that p300 might modulate the activity of the TR—RxR—MEF2A complex by recruiting a hypothetical endogenous inhibitor which may act like adenovirus E1A.

Senkyunolide I Relieves Neuropathic Pain Induced by Chronic Constriction Injury by Inhibiting Activation of Microglia

2021 ◽  
Vol 20 (2) ◽  
pp. 253-258
Author(s):  
Xiaomin Huang ◽  
Miao Huo
Keyword(s):  
Neuropathic Pain ◽  
Chronic Constriction Injury ◽  
Biological Activities ◽  
Bioactive Components ◽  
Extracellular Signal Regulated Kinase ◽  
Extracellular Signal ◽  
Induced Apoptosis ◽  
Kinase Pathway ◽  
Senkyunolide I

As an alternative to the use of narcotics, generally refractory to long-term effectiveness, for the management of neuropathic pain, we have explored the utility of senkyunolide I. Senkyunolide I is one of the bioactive components isolated from Ligusticum chuanxiong Hort known to exhibit multiple biological activities. In this study, we report senkyunolide I inhibition of chronic constriction injury induced neuropathic pain. Mechanistically, senkyunolide I inhibited chronic constriction injury induced apoptosis and the activity of microglia via extracellular signal regulated kinase pathway. We therefore suggest that senkyunolide I could serve as a promising drug for the treatment of neuropathic pain.

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