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Full-Text Articles in Diseases
Quantitative Phosphoproteomic Analysis Reveals Unique Camp Signaling Pools Emanating From Ac2 And Ac6 In Human Airway Smooth Muscle Cells, Isabella Cattani-Cavalieri, Yue Li, Jordyn Margolis, Amy S. Bogard, Moom R. Roosan, Rennolds S. Ostrom
Quantitative Phosphoproteomic Analysis Reveals Unique Camp Signaling Pools Emanating From Ac2 And Ac6 In Human Airway Smooth Muscle Cells, Isabella Cattani-Cavalieri, Yue Li, Jordyn Margolis, Amy S. Bogard, Moom R. Roosan, Rennolds S. Ostrom
Pharmacy Faculty Articles and Research
Human airway smooth muscle (HASM) is the primary target of ßAR agonists used to control airway hypercontractility in asthma and chronic obstructive pulmonary disease (COPD). ßAR agonists induce the production of cAMP by adenylyl cyclases (ACs), activate PKA and cause bronchodilation. Several other G-protein coupled receptors (GPCR) expressed in human airway smooth muscle cells transduce extracellular signals through cAMP but these receptors elicit different cellular responses. Some G-protein coupled receptors couple to distinct adenylyl cyclases isoforms with different localization, partly explaining this compartmentation, but little is known about the downstream networks that result. We used quantitative phosphoproteomics to define the …
Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez
Identifying A Glucocorticoid-Activated Gpcr That Rapidly And Non-Genomically Increases Camp Levels In Mammalian Cells, Francisco Nunez
Pharmaceutical Sciences (PhD) Dissertations
Glucocorticoids (GCs) are steroid hormones that regulate diverse physiological processes. Synthetic versions of GCs are commonly used to treat inflammatory diseases such as asthma by modulating gene expression to suppressing several inflammatory activities. However, it is estimated that 5-10% of asthmatics are unresponsive to GCs, which may be explained by receptor desensitization and/or the presence of a neutrophilic endotype. One understudied phenomenon of GCs is their ability to induce rapid, non-genomic actions. For example, GCs can acutely modulate calcium concentrations levels, induce smooth muscle relaxation and modulate nitric oxide synthase activity, within minutes and sometimes seconds, which is too rapid …
Phosphodiesterase Isoforms And Camp Compartments In The Development Of New Therapies For Obstructive Pulmonary Diseases, Martina Schmidt, Isabella Cattani-Cavalieri, Francisco J. Nuñez, Rennolds S. Ostrom
Phosphodiesterase Isoforms And Camp Compartments In The Development Of New Therapies For Obstructive Pulmonary Diseases, Martina Schmidt, Isabella Cattani-Cavalieri, Francisco J. Nuñez, Rennolds S. Ostrom
Pharmacy Faculty Articles and Research
The second messenger molecule 3′5′-cyclic adenosine monophosphate (cAMP) imparts several beneficial effects in lung diseases such as asthma, chronic obstructive pulmonary disease (COPD) and idiopathic pulmonary fibrosis (IPF). While cAMP is bronchodilatory in asthma and COPD, it also displays anti-fibrotic properties that limit fibrosis. Phosphodiesterases (PDEs) metabolize cAMP and thus regulate cAMP signaling. While some existing therapies inhibit PDEs, there are only broad family specific inhibitors. The understanding of cAMP signaling compartments, some centered around lipid rafts/caveolae, has led to interest in defining how specific PDE isoforms maintain these signaling microdomains. The possible altered expression of PDEs, and thus abnormal …