Recent experiments show that the microtubule-associated protein (MAP) 1B is a major phosphorylation substrate for the serine/threonine kinase glycogen synthase kinase-3beta (GSK-3beta) in differentiating neurons. GSK-3beta phosphorylation of MAP1B appears to act as a molecular switch regulating the control that MAP1B exerts on microtubule dynamics in growing axons and growth cones. Maintaining a population of dynamically unstable microtubules in growth cones is important for axon growth and growth cone pathfinding. We have mapped two GSK-3beta phosphorylation sites on mouse MAP1B to Ser1260 and Thr1265 using site-directed point mutagenesis of recombinant MAP1B proteins, in vitro kinase assays and phospho-specific antibodies. We raised phospho-specific polyclonal antibodies to these two sites and used them to show that MAP1B is phosphorylated by GSK-3beta at Ser1260 and Thr1265 in vivo. We also showed that in the developing nervous system of rat embryos, the expression of GSK-3beta phosphorylated MAP1B is spatially restricted to growing axons, in a gradient that is highest distally, despite the expression of MAP1B and GSK-3beta throughout the entire neuron. This suggests that there is a mechanism that spatially regulates the GSK-3beta phosphorylation of MAP1B in differentiating neurons. Heterologous cell transfection experiments with full-length MAP1B, in which either phosphorylation site was separately mutated to a valine or, in a double mutant, in which both sites were mutated, showed that these GSK-3beta phosphorylation sites contribute to the regulation of microtubule dynamics by MAP1B.
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http://dx.doi.org/10.1242/jcs.01697 | DOI Listing |
Cell Biol Toxicol
December 2024
Department of Cardiology, Laboratory of Heart Center, Zhujiang Hospital, Southern Medical University, No 253, Middle Gongye Avenue, 510282, Guangzhou, Guangdong, People's Republic of China.
Doxorubicin-induced cardiotoxicity (DIC) poses a threat to the health and prognosis of cancer patients. It is important to find a safe and effective method for the prevention and treatment of DIC. eEF2K, which is a highly conserved α-kinase, is thought to be a therapeutic target for several human diseases.
View Article and Find Full Text PDFJ Cannabis Res
December 2024
Department of Anatomy, College of Medicine, King Khalid University, Abha, 62529, Saudi Arabia.
Angiogenesis is an intrinsic physiological process involving the formation of new capillaries from existing ones. Synthetic cannabinoids refer to a class of human-made chemicals that are primarily designed to mimic the effects of delta-9-tetrahydrocannabinol, the primary psychoactive compound in cannabis. Studies investigating the association between synthetic cannabinoids and cellular reactions are limited, and the available scientific evidence is insufficient.
View Article and Find Full Text PDFZhongguo Zhong Yao Za Zhi
November 2024
Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine Shanghai 200437, China.
Through in vitro and in vivo experiments, combined with network pharmacology and molecular docking techniques, this study investigated the mechanism of action of osthole in the treatment of colorectal cancer(CRC). The relevant targets of osthole and CRC were retrieved from the SwissTargetPrediction and SuperPred in drug databases, as well as GeneCards and OMIM in disease databases. Protein-protein interaction(PPI) networks were constructed using the STRING database and Cytoscape 3.
View Article and Find Full Text PDFACS Pharmacol Transl Sci
December 2024
Department of Pharmacology, Institute of Pharmacy, Nirma University, Ahmedabad, Gujarat 382481, India.
This study aims to determine the effect of chronic hyperglycemia, induced by a high-fat diet and STZ-induced diabetes, on the development of Parkinson's disease-like characteristics. Understanding this relationship is crucial in pharmacology, neurology, and diabetes, as it could potentially lead to developing new therapeutic strategies for Parkinson's disease. Our study employed a comprehensive approach to investigate the effect of hyperglycemia on Parkinson's disease-like characteristics.
View Article and Find Full Text PDFJ Ethnopharmacol
December 2024
Department of Pulmonary and Critical Care Medicine, China-Japan Friendship Hospital, Beijing, 100029, China. Electronic address:
Ethnopharmacological Relevance: Danlong oral liquid (DLOL) is a traditional Chinese proprietary medicine commonly used to treat chronic respiratory diseases, including bronchial asthma and chronic obstructive pulmonary disease. However, the therapeutic effects and pharmacological mechanisms of DLOL in improving airway remodeling remain unclear.
Aims Of The Study: This study utilizes in vivo and in vitro experiments, serum pharmacological analysis, and network-based pharmacology approaches to investigate the effects and mechanisms of DLOL on airway remodeling and epithelial-mesenchymal transition (EMT) in asthma.
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