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Over the past decades, research has defined cAMP as one of the central cellular nodes in sensing and integrating multiple pathways and as a pivotal role player in lung pathophysiology. Obstructive lung disorders, such as chronic obstructive pulmonary disease (COPD), are characterized by a persistent and progressive airflow limitation and by oxidative stress from endogenous and exogenous insults. The extent of airflow obstruction depends on the relative deposition of different constituents of the extracellular matrix, a process related to epithelial-to-mesenchymal transition, and which subsequently results in airway fibrosis. Oxidative stress from endogenous and also from exogenous sources causes a profound worsening of COPD. Here we describe how cAMP scaffolds and their different signalosomes in different subcellular compartments may contribute to COPD. Future research will require translational studies to alleviate disease symptoms by pharmacologically targeting the cAMP scaffolds. LINKED ARTICLES: This article is part of a themed section on Adrenoceptors-New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc.
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http://dx.doi.org/10.1111/bph.14605 | DOI Listing |
Biochem Pharmacol
September 2025
Section on Molecular Neuroscience, NIMH-IRP, Bethesda, MD, USA. Electronic address:
The PACAP receptor PAC1 is a G-coupled family B1 GPCR for which the highest-affinity endogenous peptide ligands are the pituitary adenylate cyclase-activating peptides PACAP38 and PACAP27, and whose most abundant endogenous ligand is PACAP38. PACAP action at PAC1 is implicated in neuropsychiatric disorders, atherosclerosis, pain chronification, and protection from neurodegeneration and ischemia. As PACAP also interacts with two related receptors, VPAC1 and VPAC2, highly selective ligands, both agonists and antagonists, for PAC1 have been sought.
View Article and Find Full Text PDFJ Biol Chem
August 2025
Division of Pulmonary and Critical Care Medicine, Department of Medicine, Cedars-Sinai Medical Center, Los Angeles, CA, 90048, USA. Electronic address:
Guanylate cyclase 2C (GCC) upon binding to the bacterial heat-stable enterotoxin ST, generates excessive cGMP, driving intestinal chloride and fluid secretion that manifests as diarrhea. We investigated the regulatory mechanism of GCC through its interactions with Scaffolding proteins sodium-hydrogen exchanger regulatory factor (NHERF)1-4. PSD95, Dlg1, ZO-1 (PDZ) domain in NHERF4 inhibited GCC catalytic activity while NHERF1-3 binary binding had no impact.
View Article and Find Full Text PDFCurr Res Food Sci
June 2025
NutriFOODChem, Department of Food Technology, Safety and Health, Ghent University, Ghent, Belgium.
Large-scale production of cultured meat requires muscle cell culture in bioreactors, where microcarriers (MCs) support cell attachment, growth, and differentiation. However, most MCs are composed of inedible materials, requiring a cell detachment step, and/or contain animal-derived components, which are undesirable for cultured meat production. Therefore, we developed animal-free edible microcarriers based on soy protein isolate (SPI) that support muscle cell growth.
View Article and Find Full Text PDFbioRxiv
May 2025
Department of Integrative Biology and Pharmacology, The University of Texas Health Science Center, Houston, Texas, USA.
Exchange protein directly activated by cAMP (EPAC1), a multifunctional intracellular cAMP receptor, dynamically localizes to various cellular loci, engaging with diverse molecular partners to maintain cellular homeostasis. The study investigates the role of the SUMO interacting motif (SIM) in the subcellular targeting and cellular functions of EPAC1. It reveals that the SIM is a critical structural element for EPAC1's association with RanBP2/Nup358, a nucleoporin of the cytoplasmic filament component of the nuclear pore complex (NPC).
View Article and Find Full Text PDFAdv Sci (Weinh)
June 2025
Institutes of Biomedical Sciences, School of Medicine, Hubei Key Laboratory of Cognitive and Affective Disorders, Jianghan University, Wuhan, 430056, China.
High-salt (HS) diet is an established risk factor for cognitive impairment, but the underlying mechanisms remain unclear. This study reveals that HS diet reduces SHANK1, a key postsynaptic scaffolding protein, via downregulation of the PKA/CREB pathway, leading to synaptic dysfunction and cognitive deficits in rats. RNA sequencing of HS-fed rat hippocampi showed downregulation of cAMP signaling and SHANK1 expression.
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