scholarly journals Direct, gabapentin-insensitive interaction of a soluble form of the calcium channel subunit α2δ-1 with thrombospondin-4

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Ehab El-Awaad ◽  
Galyna Pryymachuk ◽  
Cora Fried ◽  
Jan Matthes ◽  
Jörg Isensee ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Potential Role ◽  
Binding Assay ◽  
Molecular Level ◽  
Biochemical Properties ◽  
Matrix Proteins ◽  
Soluble Form ◽  
Voltage Gated Calcium Channels ◽  
Thrombospondin 4

Abstract The α2δ‐1 subunit of voltage-gated calcium channels binds to gabapentin and pregabalin, mediating the analgesic action of these drugs against neuropathic pain. Extracellular matrix proteins from the thrombospondin (TSP) family have been identified as ligands of α2δ‐1 in the CNS. This interaction was found to be crucial for excitatory synaptogenesis and neuronal sensitisation which in turn can be inhibited by gabapentin, suggesting a potential role in the pathogenesis of neuropathic pain. Here, we provide information on the biochemical properties of the direct TSP/α2δ-1 interaction using an ELISA-style ligand binding assay. Our data reveal that full-length pentameric TSP-4, but neither TSP-5/COMP of the pentamer-forming subgroup B nor TSP-2 of the trimer-forming subgroup A directly interact with a soluble variant of α2δ-1 (α2δ-1S). Interestingly, this interaction is not inhibited by gabapentin on a molecular level and is not detectable on the surface of HEK293-EBNA cells over-expressing α2δ‐1 protein. These results provide biochemical evidence that supports a specific role of TSP-4 among the TSPs in mediating the binding to neuronal α2δ‐1 and suggest that gabapentin does not directly target TSP/α2δ-1 interaction to alleviate neuropathic pain.

Increase of interleukin-6 mRNA in the spinal cord following peripheral nerve injury in the rat: potential role of IL-6 in neuropathic pain

1998 ◽  
Vol 62 (2) ◽  
pp. 228-235 ◽  
Author(s):  
Janice L Arruda ◽  
Raymond W Colburn ◽  
Amy J Rickman ◽  
Maria D Rutkowski ◽  
Joyce A DeLeo
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Peripheral Nerve ◽  
Nerve Injury ◽  
Interleukin 6 ◽  
Peripheral Nerve Injury ◽  
Potential Role

scholarly journals Epigenetics of aging and disease: a brief overview

2019 ◽  
Author(s):  
Christina Pagiatakis ◽  
Elettra Musolino ◽  
Rosalba Gornati ◽  
Giovanni Bernardini ◽  
Roberto Papait
Keyword(s):  
Gene Expression ◽  
Neurodegenerative Disorders ◽  
Potential Role ◽  
Molecular Level ◽  
Physiological Function ◽  
Regulate Gene Expression ◽  
Age Related ◽  
Genetic And Environmental Factors ◽  
Different Tissues

AbstractAging is an important risk factor for several human diseases such as cancer, cardiovascular disease and neurodegenerative disorders, resulting from a combination of genetic and environmental factors (e.g., diet, smoking, obesity and stress), which, at molecular level, cause changes in gene expression underlying the decline of physiological function. Epigenetics, which include mechanisms regulating gene expression independently of changes to DNA sequence, regulate gene expression by modulating the structure of chromatin or by regulating the binding of transcriptional machinery to DNA. Several studies showed that an impairment of epigenetic mechanisms promotes alteration of gene expression underlying several aging-related diseases. Alteration of these mechanisms is also linked with changes of gene expression that occurs during aging processes of different tissues. In this review, we will outline the potential role of epigenetics in the onset of two age-related pathologies, cancer and cardiovascular diseases.

scholarly journals Loss of Arc attenuates the behavioral and molecular responses for sleep homeostasis in mice

2020 ◽  
Vol 117 (19) ◽  
pp. 10547-10553 ◽  
Author(s):  
Ayako Suzuki ◽  
Masashi Yanagisawa ◽  
Robert W. Greene
Keyword(s):  
Messenger Rna ◽  
Potential Role ◽  
Molecular Level ◽  
Subcellular Location ◽  
Early Gene ◽  
Wild Type ◽  
Molecular Responses ◽  
Recovery Sleep ◽  
Sleep Homeostasis

The activity-regulated cytoskeleton-associated protein (Arc) gene is a neural immediate early gene that is involved in synaptic downscaling and is robustly induced by prolonged wakefulness in rodent brains. Converging evidence has led to the hypothesis that wakefulness potentiates, and sleep reduces, synaptic strengthening. This suggests a potential role for Arc in these and other sleep-related processes. However, the role of Arc in sleep remains unknown. Here, we demonstrated that Arc is important for the induction of multiple behavioral and molecular responses associated with sleep homeostasis. Arc knockout (KO) mice displayed increased time spent in rapid eye movement (REM) sleep under baseline conditions and marked attenuation of sleep rebound to both 4 h of total sleep deprivation (SD) and selective REM deprivation. At the molecular level, the following homeostatic sleep responses to 4-h SD were all blunted in Arc KO mice: increase of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor GluA1 and its phosphorylation in synaptoneurosomes; induction of a subset of SD-response genes; and suppression of the GluA1 messenger RNA in the cortex. In wild-type brains, SD increased Arc protein expression in multiple subcellular locations, including the nucleus, cytoplasm, and synapse, which is reversed in part by recovery sleep. Arc is critical for these behavioral and multiple molecular responses to SD, thus providing a multifunctional role for Arc in the maintenance of sleep homeostasis, which may be attributed by the sleep/wake-associated changes in subcellular location of Arc.

scholarly journals The Potential Role of Intrathecal Nefopam in the Management of Neuropathic Pain

2014 ◽  
Vol 27 (3) ◽  
pp. 301 ◽  
Author(s):  
Mohamed Amin Ghobadifar ◽  
Navid Kalani
Keyword(s):  
Neuropathic Pain ◽  
Potential Role

The potential role of nerve growth factor in cryoneurolysis-induced neuropathic pain in rats

Cryobiology ◽  
2012 ◽  
Vol 65 (2) ◽  
pp. 132-138 ◽  
Author(s):  
Hui Ju ◽  
Yi Feng ◽  
Zhifeng Gao ◽  
Ba-Xian Yang
Keyword(s):  
Neuropathic Pain ◽  
Nerve Growth Factor ◽  
Growth Factor ◽  
Potential Role ◽  
Nerve Growth

scholarly journals Acinetobacter baumanniiLipopolysaccharide Influences Adipokine Expression in 3T3-L1 Adipocytes

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Yuka Unno ◽  
Yoshinori Sato ◽  
Satoshi Nishida ◽  
Akiyo Nakano ◽  
Ryuichi Nakano ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Potential Role ◽  
Molecular Level ◽  
Opportunistic Pathogen ◽  
Lipocalin 2 ◽  
Increased Risk ◽  
Adipocyte Cell

Acinetobacter baumanniiis one of the most important nosocomial opportunistic pathogen worldwide. In addition, obesity has been associated with an increased risk of nosocomial infection, suggesting that there may be an association betweenA. baumanniiand white adipose tissue. However, the effects ofA. baumanniion adipocytes have not been well studied at the molecular level. Here, we investigated the potential role ofA. baumannii-derived lipopolysaccharides (LPS) as signaling molecules that affect adipocyte functionality. We tested the effect of increasing concentrations ofA. baumannii-derived LPS (10, 100, or 1000 ng/mL) on the 3T3-L1 adipocyte cell line. Exposure to LPS was found to increase the expression of several adipokines (e.g., MIP-2, MCP-1, TNF-α, IL-6, lipocalin-2, and FABP4) in 3T3-L1 adipocytes and significantly reduced the expression of leptin and adiponectin. The effects ofA. baumannii-derived LPS on MIP-2 expression were similar in comparison with that of LPS prepared fromPseudomonas aeruginosaandEscherichia coliin our cell culture-based system. This study suggests thatA. baumannii-derived LPS functions as a signaling molecule that impacts the inflammatory function of white adipose tissue on the level of gene expression.

scholarly journals Connective Tissue Growth Factor in Normal and Pathological Processes

2020 ◽  
Vol 10 (4) ◽  
pp. 254-261
Author(s):  
S. V. Topolyanskaya
Keyword(s):  
Growth Factor ◽  
Connective Tissue ◽  
Connective Tissue Growth Factor ◽  
Potential Role ◽  
Tissue Growth ◽  
Matrix Proteins ◽  
Cellular Functions ◽  
Different Types ◽  
Oncological Diseases

Modern concepts about the role of connective tissue growth factor in various physiological and pathological processes are described in the review. Connective tissue growth factor regulates a variety of cellular functions, including proliferation, migration, adhesion, differentiation and synthesis of extracellular matrix proteins in cells of different types. This factor is also involved in more complex biological processes of angiogenesis, chondrogenesis, wound healing, fibrosis and oncogenesis. Increased expression of connective tissue growth factor is observed in different cardiovascular and oncological diseases. Potential role of this growth factor in regulation of cellular senescence and aging processes is also discussed.

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