scholarly journals Investigating the Role of Porcupine and WNTless: Components of WNT Signalling Pathway in Response to Endoplasmic Reticulum, Oxidative, Hypoxia and Environmental Toxins Stesses

2021 ◽  
Author(s):  
Rowida Mohamed
Author(s):  
Rubin S Baskir ◽  
Amanda G Hansen ◽  
Ethan Lee

2009 ◽  
Vol 126 ◽  
pp. S156
Author(s):  
Laura L. Yates ◽  
Carsten Schnatwinkel ◽  
Jennifer N. Murdoch ◽  
Debora Bogani ◽  
Caroline J. Formstone ◽  
...  

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Meng Li ◽  
Weiman Gao ◽  
Le Ji ◽  
Jia Li ◽  
Wanting Jiang ◽  
...  

Objective. Methane saline (MS) can be used to treat many diseases via its anti-inflammatory, antiapoptotic, and antioxidative activities. However, to date, there is no published evidence as to whether MS has any effect on traumatic brain injury (TBI). The Wnt signalling pathway regulates cell proliferation, differentiation, migration, and apoptosis; however, whether the Wnt signalling pathway regulates any effect of MS on TBI is unknown. This study was designed to explore the role of MS in the treatment of TBI and whether the Wnt pathway is involved. Methods. Sprague-Dawley rats were randomly divided into five groups: sham, TBI, TBI+10 ml/kg MS, TBI+20 ml/kg MS, and TBI+30 ml/kg MS. After induction of TBI, MS was injected intraperitoneally once daily for seven consecutive days. Neurological function was evaluated by the Neurological Severity Score (NSS) at 1, 7, and 14 days after TBI. Haematoxylin-eosin (HE) staining, inflammatory factors, neuron-specific enolase (NSE) staining, oxidative stress, and cell apoptosis were measured and compared 14 d after TBI to identify the optimal dose of MS and to investigate the effect of MS on TBI. In the second experiment, Sprague-Dawley rats were randomly divided into four groups: sham, TBI, TBI+20 ml/kg MS, and TBI+20 ml/kg MS+Dickkopf-1 (DKK-1, a specific inhibitor of the Wnt pathway). NSE, caspase-3, superoxide dismutase (SOD), Wnt3a, and β-catenin were detected by real-time PCR and Western blotting. The results from each group were compared 14 d after TBI to determine the regulatory role of the Wnt pathway. Results. Methane saline significantly inhibited inflammation, oxidative stress, and cell apoptosis, thus protecting neurons within 14 days of TBI. The best treatment effect against TBI was obtained with 20 ml/kg MS. When the Wnt pathway was inhibited, the treatment effect of MS was impaired. Conclusion. Methane saline ameliorates TBI through its anti-inflammatory, antiapoptotic, and antioxidative effects via activation of the Wnt signalling pathway, which plays a part but is not the only mechanism underlying the effects of MS. Thus, MS may be a novel strategy for treating TBI.


2016 ◽  
Author(s):  
Κωνσταντίνος Ψαρρός

Το Wnt σηματοδοτικό μονοπάτι αποτελεί τον κύριο ρυθμιστή για μια πληθώρα κυτταρικών διεργασιών. Πρόσφατα δύο «μη κανονικά» Wnt σηματοδοτικά μονοπάτια. Αυτά είναι γνωστά ως το Planar Cell Polarity pathway (PCP) και το Calcium dependant pathway (CDP). Το Wnt5a είναι μια πρωτεΐνη που ενεργοποιεί εκλεκτικά τα μη κανονικά Wnt σηματοδοτικά μονοπάτια, ενώ ρυθμιστής της αποτελεί το Sfrp5. Ο ρόλος τους στο καρδιαγγειακό σύστημα και πιο συγκεκριμένα στην οξειδοαναγωγική κατάσταση του μυοκαρδίου δεν έχει ακόμα εξερευνηθεί.Η εξωγενής χορήγηση Wnt5a αλλά και η ενδογενής υπερέκφραση του σε κύτταρα H9C2 οδήγησαν σε αυξημένη παραγωγή υπεροξειδικών ριζών προερχόμενων από το ένζυμο NADPH οξειδάση. Επιπλέον η εξωγενής χορήγηση wnt5a ενεργοποιεί το CDP μέσω της CamKII αλλά και του PCP μέσω του Rac1. Επιπλέον, στο κυτταρικό μοντέλο υπερέκφρασης του Wnt5a παρατηρήθηκε και φωσφωρυλίωση της JNK αλλά και υπερτροφικός φαινότυπος κατά την διαφοροποίησή τους λόγω αυξημένης συγκέντρωσης ενδοκυτταρικού ασβεστίου. Τα αποτελέσματα επιβεβαιώθηκαν περεταίρω και με την χρήση αναστολέων για το μονοπάτι CDP και του PCP. Τα αποτελέσματα της έρευνας αυτής υποδεικνύουν τον ρόλο του Wnt5a ως ρυθμιστή της οξειδοαναγωγικής κατάστασης στην καρδιά, καθιστώντας τo Wnt5a και τα μη κανονικά Wnt σηματοδοτικά μονοπάτια πιθανούς θεραπευτικούς στόχους για το οξειδωτικό στρες και την καρδιακή υπερτροφία.


2021 ◽  
Vol 22 (19) ◽  
pp. 10840
Author(s):  
Jasna Lojk ◽  
Janja Marc

The Wnt signalling pathway is one of the central signalling pathways in bone development, homeostasis and regulation of bone mineral density. It consists of numerous Wnt ligands, receptors and co-receptors, which ensure tight spatiotemporal regulation of Wnt signalling pathway activity and thus tight regulation of bone tissue homeostasis. This enables maintenance of optimal mineral density, tissue healing and adaptation to changes in bone loading. While the role of the canonical/β-catenin Wnt signalling pathway in bone homeostasis is relatively well researched, Wnt ligands can also activate several non-canonical, β-catenin independent signalling pathways with important effects on bone tissue. In this review, we will provide a thorough overview of the current knowledge on different non-canonical Wnt signalling pathways involved in bone biology, focusing especially on the pathways that affect bone cell differentiation, maturation and function, processes involved in bone tissue structure regulation. We will describe the role of the two most known non-canonical pathways (Wnt/planar cell polarity pathways and Wnt/Ca2+ pathway), as well as other signalling pathways with a strong role in bone biology that communicate with the Wnt signalling pathway through non-canonical Wnt signalling. Our goal is to bring additional attention to these still not well researched but important pathways in the regulation of bone biology in the hope of prompting additional research in the area of non-canonical Wnt signalling pathways.


2001 ◽  
Vol 359 (1) ◽  
pp. 1-16 ◽  
Author(s):  
Sheelagh FRAME ◽  
Philip COHEN

Identified originally as a regulator of glycogen metabolism, glycogen synthase kinase-3 (GSK3) is now a well-established component of the Wnt signalling pathway, which is essential for setting up the entire body pattern during embryonic development. It may also play important roles in protein synthesis, cell proliferation, cell differentiation, microtubule dynamics and cell motility by phosphorylating initiation factors, components of the cell-division cycle, transcription factors and proteins involved in microtubule function and cell adhesion. Generation of the mouse knockout of GSK3β, as well as studies in neurons, also suggest an important role in apoptosis. The substrate specificity of GSK3 is unusual in that efficient phosphorylation of many of its substrates requires the presence of another phosphorylated residue optimally located four amino acids C-terminal to the site of GSK3 phosphorylation. Recent experiments, including the elucidation of its three-dimensional structure, have enhanced our understanding of the molecular basis for the unique substrate specificity of GSK3. Insulin and growth factors inhibit GSK3 by triggering its phosphorylation, turning the N-terminus into a pseudosubstrate inhibitor that competes for binding with the ‘priming phosphate’ of substrates. In contrast, Wnt proteins inhibit GSK3 in a completely different way, by disrupting a multiprotein complex comprising GSK3 and its substrates in the Wnt signalling pathway, which do not appear to require a ‘priming phosphate’. These latest findings have generated an enormous amount of interest in the development of drugs that inhibit GSK3 and which may have therapeutic potential for the treatment of diabetes, stroke and Alzheimer's disease.


2003 ◽  
Vol 89 (7) ◽  
pp. 1298-1304 ◽  
Author(s):  
K Rask ◽  
A Nilsson ◽  
M Brännström ◽  
P Carlsson ◽  
P Hellberg ◽  
...  

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