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acetylcholine wnt

Seung-Ryeol Lee, Ki-Ho Kim, Ho-Song You, Johnny Fu, Tung-Chin Mike Hsieh, Valmik Bhargava, M Raj Rajasekaran
Current technology for penile hemodynamic evaluations in small animals is invasive and has limitations. We evaluated a novel laser speckle contrast imaging (LSCI) technique to determine age-related changes in penile microvascular perfusion (PMP) and tested the role of cavernosal muscle (CC) fibrosis mediated by Wnt-TGF β1 signaling pathways in a mouse model. Ten young (2-3 months) and old (24-28 months) wild-type C57BL6 male mice were subjected to PMP measured using a LSCI system. Penile blood flow (PBF, peak systolic velocity, PSV) was also measured using a color Doppler ultrasound for comparison...
November 2017: Physiological Reports
Miranda L Xu, Cathy W C Bi, Etta Y L Liu, Tina T X Dong, Karl W K Tsim
Acetylcholinesterase (AChE) hydrolyzes acetylcholine to terminate cholinergic transmission in neurons. Apart from this AChE activity, emerging evidence suggests that AChE could also function in other, non-neuronal cells. For instance, in bone, AChE exists as a proline-rich membrane anchor (PRiMA)-linked globular form in osteoblasts, in which it is proposed to play a noncholinergic role in differentiation. However, this hypothesis is untested. Here, we found that in cultured rat osteoblasts, AChE expression was increased in parallel with osteoblastic differentiation...
July 28, 2017: Journal of Biological Chemistry
Yuan Liu, Shuai Hao, Beibei Yang, Yi Fan, Xiaodong Qin, Yun Chen, Jun Hu
Parkinson's disease (PD) is a neurodegenerative disorder with an incidence second only to Alzheimer's disease. The main pathological feature of PD is the death of dopaminergic neurons in the substantia nigra pars compacta. Nicotinic receptor agonists are neuroprotective in several PD models and there is considerable evidence that α7 nicotinic acetylcholine receptors (α7-nAChRs) are important therapeutic targets for neurodegenerative diseases. However, the involvement of α7-nAChRs and underlying signaling mechanisms in PD pathogenesis are unclear...
September 15, 2017: Biochemical Pharmacology
Chengze Wang, Xin Xu, Hairu Jin, Gangli Liu
To investigate the effects and the possible underlying mechanisms of nicotine stimulation on tongue squamous cell carcinoma (TSCC) progression, a TSCC cell line Cal27 and 34 samples of paraffin-embedded TSCC were examined. Immunofluorescence, western blot analysis, and TOP/FOP flash, CCK-8, wound healing and Transwell invasion assays were used to evaluate Cal27 in response to nicotine stimulation. We also investigated expression levels of related proteins of Wnt/β-catenin and Wnt/PCP pathways in paraffin-embedded TSCC samples with or without a history of smoking by immunohistochemistry...
May 2017: Oncology Letters
Pratima Pandey, Ashwani Bhardwaj, Kavita Babu
Perturbations in synaptic function could affect the normal behavior of an animal, making it important to understand the regulatory mechanisms of synaptic signaling. Previous work has shown that in Caenorhabditis elegans an immunoglobulin superfamily protein, RIG-3, functions in presynaptic neurons to maintain normal acetylcholine receptor levels at the neuromuscular junction (NMJ). In this study, we elucidate the molecular and functional mechanism of RIG-3. We demonstrate by genetic and BiFC (Bi-molecular Fluorescence Complementation) assays that presynaptic RIG-3 functions by directly interacting with the immunoglobulin domain of the nonconventional Wnt receptor, ROR receptor tyrosine kinase (RTK), CAM-1, which functions in postsynaptic body-wall muscles...
July 2017: Genetics
Julien Messéant, Jérôme Ezan, Perrine Delers, Konstantin Glebov, Carmen Marchiol, Franck Lager, Gilles Renault, Fadel Tissir, Mireille Montcouquiol, Nathalie Sans, Claire Legay, Laure Strochlic
Understanding the developmental steps that shape formation of the neuromuscular junction (NMJ) connecting motoneurons to skeletal muscle fibers is crucial. Wnt morphogens are key players in the formation of this specialized peripheral synapse, but their individual and collaborative functions and downstream pathways remain poorly understood at the NMJ. Here, we demonstrate through Wnt4 and Wnt11 gain-of-function studies in cell culture or in mice that Wnts enhance acetylcholine receptor (AChR) clustering and motor axon outgrowth...
May 1, 2017: Development
Michelle Monje
The nervous system is emerging as a regulator of malignancy. In this issue of Cancer Cell, Hayakawa et al. demonstrate a feedforward signaling loop in which tumor-derived nerve growth factor promotes enteric tumor innervation, and recruited nerves drive cancer growth through acetylcholine-regulated Wnt signaling and stimulation of further NGF release.
January 9, 2017: Cancer Cell
Kinji Ohno, Mohammad Alinoor Rahman, Mohammad Nazim, Farhana Nasrin, Yingni Lin, Jun-Ichi Takeda, Akio Masuda
We humans have evolved by acquiring diversity of alternative RNA metabolisms including alternative means of splicing and transcribing non-coding genes, and not by acquiring new coding genes. Tissue-specific and developmental stage-specific alternative RNA splicing is achieved by tightly regulated spatiotemporal regulation of expressions and activations of RNA-binding proteins that recognize their cognate splicing cis-elements on nascent RNA transcripts. Genes expressed at the neuromuscular junction are also alternatively spliced...
August 2017: Journal of Neurochemistry
Hiroaki Nakashima, Bisei Ohkawara, Shinsuke Ishigaki, Takayasu Fukudome, Kenyu Ito, Mikito Tsushima, Hiroyuki Konishi, Tatsuya Okuno, Toshiro Yoshimura, Mikako Ito, Akio Masuda, Gen Sobue, Hiroshi Kiyama, Naoki Ishiguro, Kinji Ohno
At the neuromuscular junction (NMJ), acetylcholine receptor (AChR) clustering is mediated by spinal motor neuron (SMN)-derived agrin and its receptors on the muscle, the low-density lipoprotein receptor-related protein 4 (LRP4) and muscle-specific receptor tyrosine kinase (MuSK). Additionally, AChR clustering is mediated by the components of the Wnt pathway. Laser capture microdissection of SMNs revealed that a secreted activator of Wnt signaling, R-spondin 2 (Rspo2), is highly expressed in SMNs. We found that Rspo2 is enriched at the NMJ, and that Rspo2 induces MuSK phosphorylation and AChR clustering...
2016: Scientific Reports
Leonor Remédio, Katherine D Gribble, Jennifer K Lee, Natalie Kim, Peter T Hallock, Nicolas Delestrée, George Z Mentis, Robert C Froemke, Michael Granato, Steven J Burden
Motor axons approach muscles that are prepatterned in the prospective synaptic region. In mice, prepatterning of acetylcholine receptors requires Lrp4, a LDLR family member, and MuSK, a receptor tyrosine kinase. Lrp4 can bind and stimulate MuSK, strongly suggesting that association between Lrp4 and MuSK, independent of additional ligands, initiates prepatterning in mice. In zebrafish, Wnts, which bind the Frizzled (Fz)-like domain in MuSK, are required for prepatterning, suggesting that Wnts may contribute to prepatterning and neuromuscular development in mammals...
May 1, 2016: Genes & Development
Kinji Ohno, Kenji Otsuka, Mikako Ito
The low-density lipoprotein receptor-related protein 4 (LRP4) and the muscle-specific receptor tyrosine kinase (MuSK) form a tetrameric protein complex on the postsynaptic membrane at the neuromuscular junction (NMJ). Binding of agrin to LRP4 triggers phosphorylation of MuSK. Activated MuSK drives clustering of acetylcholine receptor (AChR). Wnt ligands also directly bind to MuSK to induce AChR clustering. MuSK anchors the acetylcholinesterase (AChE)/collagen Q (ColQ) complex to the synaptic basal lamina. In addition, an extracellular proteoglycan, biglycan, binds to MuSK...
November 25, 2016: Chemico-biological Interactions
Morten Skøtt Thomsen, Jesper Tobias Andreasen, Maria Arvaniti, Kristi Anne Kohlmeier
Nicotinic acetylcholine receptors (nAChRs) have been pursued for decades as potential molecular targets to treat cognitive dysfunction in Alzheimer's disease (AD) due to their positioning within regions of the brain critical in learning and memory, such as the prefrontal cortex and hippocampus, and their demonstrated role in processes underlying cognition such as synaptic facilitation, and theta and gamma wave activity. Historically, activity at these receptors is facilitated in AD by use of drugs that increase the levels of their endogenous agonist acetylcholine, and more recently nAChR selective ligands have undergone clinical trials...
2016: Current Pharmaceutical Design
Stephen I Deutsch, Jessica A Burket, Maria R Urbano, Andrew D Benson
Currently, there are no medications that target core deficits of social communication and restrictive, repetitive patterns of behavior in persons with autism spectrum disorders (ASDs). Adults with Down syndrome (DS) display a progressive worsening of adaptive functioning, which is associated with Alzheimer's disease (AD)-like histopathological changes in brain. Similar to persons with ASDs, there are no effective medication strategies to prevent or retard the progressive worsening of adaptive functions in adults with DS...
October 15, 2015: Biochemical Pharmacology
De-Qi Jiang, Mei-Dan Wei, Ke-Wan Wang, Yan-Xian Lan, Ning Zhu, Yong Wang
Recent studies have demonstrated that the molecules secreted from microglias play important roles in the cell fate determination of neural stem cells (NSCs), and nicotinic acetylcholine receptor agonist treatment could reduce neuroinflammation in some neurodegenerative disease models, such as Alzheimer's disease (AD). However, it is not clear how nicotine plays a neuroprotective role in inflammation-mediated central nervous diseases, and its possible mechanisms in the process remain largely elusive. The aim of this study is to improve the survival microenvironment of NSCs co-cultured with microglias in vitro by weakening inflammation that mediated by accumulation of β-amyloid peptide (Aβ)...
2016: International Journal of Neuroscience
S Kurimoto, J Jung, M Tapadia, J Lengfeld, D Agalliu, M Waterman, T Mozaffar, R Gupta
Recent data have shown that preservation of the neuromuscular junction (NMJ) after traumatic nerve injury helps to improve functional recovery with surgical repair via matrix metalloproteinase-3 (MMP3) blockade. As such, we sought to explore additional pathways that may augment this response. Wnt3a has been shown to inhibit acetylcholine receptor (AChR) clustering via β-catenin-dependent signaling in the development of the NMJ. Therefore, we hypothesized that Wnt3a and β-catenin are associated with NMJ destabilization following traumatic denervation...
May 21, 2015: Neuroscience
Farhana Nasrin, Mohammad Alinoor Rahman, Akio Masuda, Kenji Ohe, Jun-Ichi Takeda, Kinji Ohno
Muscle specific receptor tyrosine kinase (MuSK) is an essential postsynaptic transmembrane molecule that mediates clustering of acetylcholine receptors (AChR). MUSK exon 10 is alternatively skipped in human, but not in mouse. Skipping of this exon disrupts a cysteine-rich region (Fz-CRD), which is essential for Wnt-mediated AChR clustering. To investigate the underlying mechanisms of alternative splicing, we exploited block-scanning mutagenesis with human minigene and identified a 20-nucleotide block that contained exonic splicing silencers...
2014: Scientific Reports
Chun-Mei Zhao, Yoku Hayakawa, Yosuke Kodama, Sureshkumar Muthupalani, Christoph B Westphalen, Gøran T Andersen, Arnar Flatberg, Helene Johannessen, Richard A Friedman, Bernhard W Renz, Arne K Sandvik, Vidar Beisvag, Hiroyuki Tomita, Akira Hara, Michael Quante, Zhishan Li, Michael D Gershon, Kazuhiro Kaneko, James G Fox, Timothy C Wang, Duan Chen
The nervous system plays an important role in the regulation of epithelial homeostasis and has also been postulated to play a role in tumorigenesis. We provide evidence that proper innervation is critical at all stages of gastric tumorigenesis. In three separate mouse models of gastric cancer, surgical or pharmacological denervation of the stomach (bilateral or unilateral truncal vagotomy, or local injection of botulinum toxin type A) markedly reduced tumor incidence and progression, but only in the denervated portion of the stomach...
August 20, 2014: Science Translational Medicine
Evelyn C Avilés, Cristina Pinto, Patricia Hanna, Jorge Ojeda, Viviana Pérez, Giancarlo V De Ferrari, Pedro Zamorano, Miguel Albistur, Daniel Sandoval, Juan P Henríquez
Cumulative evidence indicates that Wnt pathways play crucial and diverse roles to assemble the neuromuscular junction (NMJ), a peripheral synapse characterized by the clustering of acetylcholine receptors (AChR) on postsynaptic densities. The molecular determinants of Wnt effects at the NMJ are still to be fully elucidated. We report here that the Wnt receptor Frizzled-9 (Fzd9) is expressed in developing skeletal muscles during NMJ synaptogenesis. In cultured myotubes, gain- and loss-of-function experiments revealed that Fzd9-mediated signaling impairs the AChR-clustering activity of agrin, an organizer of postsynaptic differentiation...
2014: Frontiers in Cellular Neuroscience
Jin-Yuan Wang, Fei Chen, Xiu-Qing Fu, Chuang-Shi Ding, Li Zhou, Xiao-Hui Zhang, Zhen-Ge Luo
During the development of vertebrate neuromuscular junction (NMJ), agrin stabilizes, whereas acetylcholine (ACh) destabilizes AChR clusters, leading to the refinement of synaptic connections. The intracellular mechanism underlying this counteractive interaction remains elusive. Here, we show that caspase-3, the effector protease involved in apoptosis, mediates elimination of AChR clusters. We found that caspase-3 was activated by cholinergic stimulation of cultured muscle cells without inducing cell apoptosis and that this activation was prevented by agrin...
March 31, 2014: Developmental Cell
Zhifei Zhou, Bei Li, Zhiwei Dong, Fen Liu, Yu Zhang, Yang Yu, Fengqing Shang, Lizheng Wu, Xiaojing Wang, Yan Jin
AIMS: Cigarette smoking is one of the high risk factors of adult chronic periodontitis and nicotine is the well established toxic substance in cigarette. However, the mechanism of nicotine induced periodontitis is still unknown. Here we studied whether nicotine impaired the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) through activating α7 nicotinic acetylcholine receptor (α7 nAChR). METHODS: hPDLSCs with multi differentiation potential and surface makers for mesenchymal stem cells were harvested by limiting dilution technique...
2013: PloS One
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