Caldesmon, an inhibitory actin binding protein, binds to actin and inhibits actin-myosin interactions, whereas caldesmon phosphorylation reverses the inhibitory effect of caldesmon on actin-myosin interactions, potentially leading to enhanced contraction. The goal of this study was to investigate the cellular signaling pathway responsible for caldesmon phosphorylation, which is involved in the regulation of the contraction induced by dexmedetomidine (DMT), an alpha-2 adrenoceptor agonist, in endothelium-denuded rat aortas. SP600125 (a c-Jun NH2-terminal kinase [JNK] inhibitor) dose-response curves were generated in aortas that were pre-contracted with DMT or phorbol 12,13-dibutyrate (PDBu), a protein kinase C (PKC) activator. Dose-response curves to the PKC inhibitor chelerythrine were generated in rat aortas pre-contracted with DMT. The effects of SP600125 and rauwolscine (an alpha-2 adrenoceptor inhibitor) on DMT-induced caldesmon phosphorylation in rat aortic vascular smooth muscle cells (VSMCs) were investigated by western blot analysis. PDBu-induced caldesmon and DMT-induced PKC phosphorylation in rat aortic VSMCs was investigated by western blot analysis. The effects of GF109203X (a PKC inhibitor) on DMT- or PDBu-induced JNK phosphorylation in VSMCs were assessed. SP600125 resulted in the relaxation of aortas that were pre-contracted with DMT or PDBu, whereas rauwolscine attenuated DMT-induced contraction. Chelerythrine resulted in the vasodilation of aortas pre-contracted with DMT. SP600125 and rauwolscine inhibited DMT-induced caldesmon phosphorylation. Additionally, PDBu induced caldesmon phosphorylation, and GF109203X attenuated the JNK phosphorylation induced by DMT or PDBu. DMT induced PKC phosphorylation in rat aortic VSMCs. These results suggest that alpha-2 adrenoceptor-mediated, DMT-induced contraction involves caldesmon phosphorylation that is mediated by JNK phosphorylation by PKC.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4202027 | PMC |
| http://dx.doi.org/10.7150/ijbs.9797 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
CALMODULIN-BINDING RECEPTOR-LIKE CYTOPLASMIC KINASE 3 regulates salt tolerance through CATALASE 2 in Arabidopsis.
Plant Physiol
December 2024
Key Laboratory of Bio-Resource and Eco-Environment of Ministry of Education, College of Life Sciences, Sichuan University, Chengdu 610064, China.
Soil salinization threatens global crop production. Here, we report that a receptor-like cytoplasmic kinase, CALMODULIN-BINDING RECEPTOR-LIKE CYTOPLASMIC KINASE 3 (CRCK3), plays an essential role in plant salt tolerance via CATALASE 2 (CAT2), a hydrogen peroxide (H2O2)-scavenging enzyme in Arabidopsis (Arabidopsis thaliana). CRCK3 was induced by salt stress, and its knockout mutant displayed a salt-sensitive phenotype compared with wild-type plants.
View Article and Find Full Text PDFDeciphering the alteration of MAP2 interactome caused by a schizophrenia-associated phosphorylation.
Neurobiol Dis
December 2024
Translational Neuroscience Program, Department of Psychiatry, University of Pittsburgh, United States of America; Department of Neurology, University of Pittsburgh, United States of America. Electronic address:
Microtubule-associated protein 2 (MAP2) is a crucial regulator of dendritic structure and neuronal function, orchestrating diverse protein interactions within the microtubule network. We have shown MAP2 is hyperphosphorylated at serine 1782 (S1782) in schizophrenia and phosphomimetic mutation of S1782 in mice (MAP2) is sufficient to impair dendritic architecture. We sought to determine how this hyperphosphorylation affects the MAP2 interactome to provide insights into the disorder's mechanisms.
View Article and Find Full Text PDFMycobacterium avium inhibits protein kinase C and MARCKS phosphorylation in human cystic fibrosis and non-cystic fibrosis cells.
PLoS One
October 2024
Department of Pediatrics, University of Florida College of Medicine, Gainesville, Florida, United States of America.
In cystic fibrosis (CF), there is abnormal translocation and function of the cystic fibrosis transmembrane conductance regulator (CFTR) and an upregulation of the epithelial sodium channel (ENaC). This leads to hyperabsorption of sodium and fluid from the airway, dehydrated mucus, and an increased risk of respiratory infections. In this study, we performed a proteomic assessment of differentially regulated proteins from CF and non-CF small airway epithelial cells (SAEC) that are sensitive to Mycobacterium avium.
View Article and Find Full Text PDFA peptide against the N-terminus of myristoylated alanine-rich C kinase substrate promotes neuronal differentiation in SH-SY5Y human neuroblastoma cells.
J Vet Med Sci
November 2024
Department of Basic Veterinary Science, Joint Faculty of Veterinary Medicine, Kagoshima University, Kagoshima, Japan.
Myristoylated alanine-rich protein kinase C substrate (MARCKS) plays crucial roles in neuronal functions and differentiation. However, specific effects of the myristoylated N-terminal sequence (MANS) peptide, a widely used MARCKS modulator comprising the initial 24 amino acids of MARCKS, on neuronal cells remain unclear. Therefore, in this study, we aimed to examine the effects and action mechanisms of the MANS peptide on SH-SY5Y human neuroblastoma cells, which served as the in vitro neuronal cell models.
View Article and Find Full Text PDFInsight in the (Phospho)proteome of Vascular Smooth Muscle Cells Derived From Patients With Abdominal Aortic Aneurysm Reveals Novel Disease Mechanisms.
Arterioscler Thromb Vasc Biol
October 2024
Department of Surgery, Amsterdam University Medical Centers, Amsterdam Cardiovascular Sciences, Location Vrije Universiteit (VU) Medical Center and Academic Medical Centre (AMC), the Netherlands (K.B.R., T.A.R.v.M., N.B., K.K.Y.).
Article Synopsis
- The study focuses on abdominal aortic aneurysm (AAA), a condition where the aorta weakens and dilates in the abdomen, aiming to understand the specific cellular mechanisms involved by analyzing proteins in vascular smooth muscle cells (VSMC) from AAA patients versus healthy donors.
- Using advanced proteomic techniques, researchers found significant differences in proteins linked to extracellular matrix remodeling, energy metabolism, and muscle contractility between AAA patients and healthy individuals.
- The research revealed changes in phosphorylation patterns affecting structural proteins like those involved in the actin cytoskeleton and signaling pathways, suggesting specific kinases like NUAK1 and MAPK7 may play crucial roles in AAA development.
Want AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!