Although hearing loss is the most common sensory deficit in Western societies, there are no successful pharmacological treatments for this disorder. Recent experiments have demonstrated that manipulation of intracellular cyclic guanosine monophosphate (cGMP) concentrations can have both beneficial and harmful effects on hearing. In this review, we will examine the role of cGMP as a key second messenger involved in many aspects of cochlear function and discuss the known functions of downstream effectors of cGMP in sound processing. The nitric oxide-stimulated soluble guanylyl cyclase system (sGC) and the two natriuretic peptide-stimulated particulate GCs (pGCs) will be more extensively covered because they have been studied most thoroughly. The cochlear GC systems are attractive targets for medical interventions that improve hearing while simultaneously representing an under investigated source of sensorineural hearing loss.
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http://dx.doi.org/10.1152/physiolgenomics.00056.2018 | DOI Listing |
Hypertension
January 2025
Cardiorenal Research Laboratory, Department of Cardiovascular Medicine, Mayo Clinic, Rochester, MN. (Xiaoyu Ma, J.C.M., D.G.M., Xiao Ma, Y.Z., S.P., Y.W., S.J.S., J.C.B.).
Background: Cardiomyocyte oxidative stress significantly contributes to the progression of hypertension-induced heart failure, highlighting the need for targeted therapies. We developed a novel peptide, NPA7, that coactivates the GC-A (guanylyl cyclase A)/cGMP and MasR (Mas receptor)/cAMP pathway. This study aimed to test NPA7's ability to inhibit oxidative stress by modulating the p62-KEAP1 (Kelch-like ECH-associated protein 1)-NRF2 (nuclear factor erythroid 2-related factor 2) pathway in human cardiomyocytes (HCMs) and a rat model of hypertension.
View Article and Find Full Text PDFBiochem Pharmacol
January 2025
Department of Pharmacology, Toxicology and Clinical Pharmacy, University of Braunschweig - Institute of Technology, Germany. Electronic address:
Soluble guanylyl cyclase (sGC) is a well-established pharmacological target for the treatment of acute angina pectoris, pulmonary hypertension and heart failure. Histidine 105 in the heme binding pocket of sGC is a crucial residue for heme binding and natural enzyme activation by NO. It was assumed that the heme-free sGC mutants α/βH105F and α/βH105A were valuable research tools for studying NO independent sGC activators.
View Article and Find Full Text PDFBMJ Open
December 2024
Clinical Research Department, Ignacio Chávez National Heart Institute, Mexico City, Mexico
Objectives: To investigate clinical characteristics, symptom profile, testing practices, treatment patterns and quality of life (QoL) among patients with pulmonary arterial hypertension (PAH) in Latin America.
Design: Data from the Adelphi Real World PAH Disease Specific Programme, a cross-sectional survey with retrospective data collection.
Setting: University/teaching hospital, regional centres, private practices and government institutions in Argentina, Brazil, Colombia and Mexico.
J Mol Neurosci
December 2024
Department of Neurosurgery, National Children's Medical Center (Shanghai), Children's Hospital of Fudan University, No.399 Wan Yuan Avenue, Minhang District, Shanghai, 201102, China.
Focal cortical dysplasia (FCD) II is a cortical malformation characterized by cortical architectural abnormalities, dysmorphic neurons, with or without balloon cells. Here, we systematically explored the pathophysiological role of the GATOR1 subunit NPRL3 variants including a novel mutation from iPSCs derived from one FCD II patient. Three FCD II children aged 0.
View Article and Find Full Text PDFJ Cachexia Sarcopenia Muscle
February 2025
Mitodicure GmbH, Kriftel, Germany.
Background: Recent studies provide strong evidence for a key role of skeletal muscle pathophysiology in myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). In a 2021 review article on the pathophysiology of ME/CFS, we postulated that hypoperfusion and ischemia can result in excessive sodium and calcium overload in skeletal muscles of ME/CFS patients to cause mitochondrial damage. Since then, experimental evidence has been provided that supports this concept.
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