Explore chapters and articles related to this topic
Sensory Neuropeptides and Bronchial Hyperresponsiveness
Published in Sami I. Said, Proinflammatory and Antiinflammatory Peptides, 2020
D. Spina, C. P. Page, J. Morley
In Wistar rats, the neutral endopeptidase inhibitor phosphoramidon augmented the airway responsiveness to inhaled acetylcholine and potentiated the ability of exogenously administered neurokinin A and substance P to augment bronchoconstrictor responses to acetylcholine (143). The ability of phosphoramidon to augment airway responsiveness to acetylcholine was abrogated by vagotomy (143), implying that an enhanced vagal reflex contributes to this response and suggesting that acetylcholine may stimulate sensory nerve endings to release neuropeptides that sensitize vagal afferents in the rat. In accord with this interpretation, acetylcholine appears to stimulate afferent nerves in the Wistar rat (172) but not in the guinea pig in vivo (171). In sensitized rats, the ability of phosphoramidon to augment airway responsiveness to acetylcholine was compromised; indeed, neutral endopeptidase activity was reduced in these animals (173).
Epithelial Function and Airway Responsiveness
Published in Alastair G. Stewart, AIRWAY WALL REMODELLING in ASTHMA, 2020
Roy G. Goldie, Janet M. H. Preuss
Epithelium denudation also caused significant potentiation of the relaxant responses to exogenously applied VIP,176 a peptide which, with NO, may be a neurotransmitter in the i-NANC nervous system.129,130,132 Similar potentiation of VIP-induced relaxation of human bronchial preparations has been reported.265 Atrial natriuretic peptide (ANP) causes airway smooth muscle relaxation,266,267 which was markedly potentiated in epithelium-denuded preparations175 (Figure 3). The neutral endopeptidase inhibitor phosphoramidon largely mimicked the potentiation observed with epithelium stripping for both VIP177 and ANP,175 further evidence that the airway epithelium has a significant capacity to act as a metabolic sink for various peptide substances. Interestingly, a tetrodotoxin-resistant i-NANC component of relaxation to EFS was reported in epithelium-intact guinea pig trachea, raising the possibility of the release of an epithelium-derived inhibitory factor.177
Is too much neurohormonal blockade harmful?
Published in ILEANA PIÑA, SIDNEY GOLDSTEIN, MARK E DUNLAP, The Year in Heart Failure, 2005
The neurohormonal model of the progression of heart failure suggests that blocking the deleterious effects of the vasoconstrictive hormones and stimulating the vasodilators would have beneficial effects, not only on haemodynamics but also on ventricular remodelling and survival. The clinical development of the dual ACE and neutral endopeptidase inhibitor omapatrilat provided the opportunity to test this hypothesis. The Omapatrilat Versus Enalapril Randomized Trial of Utility in Reducing Events (OVERTURE) compared the effects of enalapril (20 mg/day) and omapatrilat (40 mg/day) in 5770 patients with New York Heart Association class II-IV heart failure over 14.5 months who were optimally treated (50o/o on 13 blockers, 40o/o spironolactone, and 60o/o digoxin) 1221. The primary end-points of death and hospitalization for heart failure were not different in the enalapril and omapatrilat groups (hazard ratio 0.94; 95o/o CI 0.86-1.03; P = 0.187), but the study fulfilled the pre-specified criteria of non-inferiority for omapatrilat. Omapatrilat, however, did reduce the combined risk of cardiovascular deaths or hospitalization by 9o/o (P = 0.024). Although the event rate in these high-risk patients was high, the lack of incremental benefit may have been related to significant episodes of hypotension during the period of drug up-titration. A post hoc analysis of the role of baseline systolic blood pressure on the response to omapatrilat showed that omapatrilat had
RNA-Seq Analysis of Clinical Samples from TCGA Reveal Molecular Signatures for Ovarian Cancer
Published in Cancer Investigation, 2023
Rucha M. Wadapurkar, Aruna Sivaram, Renu Vyas
Most of the genes differentially expressed in recurrent tumor were found to be associated with angiogenesis, positive regulation of epithelial cell proliferation, autophagy, osteoblast differentiation, potassium ion transmembrane transport, phosphatidylinositol-4, 5-bisphosphate 3-kinase activity, TNF signalling pathway and apoptosis. For the early vs late-stage category, significant associations were found with cell adhesion, positive regulation of cell proliferation, positive regulation of ERK1 and ERK2 cascade, cell-cell signalling, female pregnancy and chemokine activity, growth factor activity and chemical carcinogenesis, whereas associations were observed with growth factor activity and serine-type endopeptidase inhibitor activity in post-menopausal women. From the PPI network analysis, hub genes were identified for each category. Though many of these hub genes were unique to each category, some common genes were also identified. CTRC, CPA2, SPINK1, CPA1 and DAZL have been observed to be differentially expressed in advanced stages of the diseases and also in patients at the post-menopausal age, signifying their potential role in progression of the disease. SLC4A4 and EGF were found to be common in advanced stages and in recurrent tumor.
Saliva proteomic profile of early childhood caries and caries-free children
Published in Acta Odontologica Scandinavica, 2023
Bethania Paludo Oliveira, Marília Afonso Rabelo Buzalaf, Natália Caldeira Silva, Talita Mendes Oliveira Ventura, Júlia Toniolo, Jonas Almeida Rodrigues
Cystatin-S, Cystatin-SN, Cystatin-SA and Cystatin-B (2-fold increase) were up-regulated in the CF group. Cystatin-S and Cystatin-SN were also correlated with the absence of caries in previous studies of saliva [4], as well as Lipocalin-1, which was also up-regulated in the CF group. Cystatin-S, Cystatin-SN and Lipocalin-1 may indirectly provide tooth protection by inhibiting proteolytic events on other salivary proteins. Additionally, Cystatin-B is an intracellular thiol proteinase inhibitor and has cysteine-type endopeptidase inhibitor activity [22]. Interestingly, the results of a functional analysis of the most affected processes in the molecular function, when comparing the CF vs ECC groups, showed that 21.9% was involved in cysteine-type endopeptidase inhibitor activity (Figure 4).
Mapping the human sperm proteome – novel insights into reproductive research
Published in Expert Review of Proteomics, 2023
Mika Alexia Miyazaki, Raquel Lozano Guilharducci, Paula Intasqui, Ricardo Pimenta Bertolla
During their journey through the female genital tract, sperm undergo functional changes in order to achieve successful fertilization. Among these processes, spermatozoa capacitation has been studied from a proteomics point of view to understand the protein pattern transition in this event. After capacitation medium (CAP) incubation, increased proteins mainly involved in fertilization, sperm motility, and energy production were observed. Between 11 proteins identified, 9 were decreased, such as AKAP3, AKAP4, ODF2, Phosphoglycerate kinase 2 (PGK2), and Radial spoke head 1 homolog (RSPH1), all of them involved in PKA-dependent signaling process and consequently in supporting sperm motility [55,70]. In order to catalyze the first ATP-generating step in the central metabolic pathway of glycolysis to promote = tail movement, PGK2 protein is necessary. Located mainly in the principal piece of the flagellum, in male Pgk2−/− mice, sperm function, and motility were found to be altered, what may be the reason for the low expression [82]. On the other hand, five proteins, mainly from signaling, protein degradation, and vesicular trafficking processes were increased [70]. Moreover, a study incubating sperm with increasing concentrations of sperm plasma membrane-associated proteins (SMAP) showed about 12 proteins associated with the sperm surface. Of these, 22% are associated with protein binding and 7% with endopeptidase inhibitor activity, and they can also affect tyrosine phosphorylation, which, in turn, affects sperm hyperactivated motility [83].