Inhibition of cAMP synthesis abolishes the impact of curcumin administration in the skeletal muscle of rodents
Robert Hofstra, Noriyuki Koibuchi, Suthat Fucharoen in Advances in Biomolecular Medicine, 2017
Skeletal muscle is a highly malleable tissue, capable of considerable metabolic and morphological adaptations in response to repeated bouts of contractile activity (i.e. exercise). It is well established that chronic contractile activity, in the form of repeated bouts of endurance exercise, usually interspersed with recovery periods, results in the altered expression of a wide variety of gene products, leading to an altered muscle phenotype with improved fatigue resistance. This improved endurance is highly correlated with the increase in muscle mitochondrial density and enzyme activity, referred to as “mitochondrial biogenesis” (Nourshahi et al., 2012). The ubiquitous second messenger cyclic AMP (cAMP) and its cellular effector Protein Kinase A (PKA) constitute one of the most widely studied signaling cascades. In both mammalian cells and yeast, the regulation of mitochondrial biogenesis clearly involves the cAMP signaling pathway (Yoboue et al., 2012). Protein Kinase A (PKA), also known as the cAMP-dependent enzyme, is a well-studied, downstream effector of cAMP and is activated only in the presence of cAMP. Activated PKA phosphorylates a number of other proteins including cAMP Response Element Binding protein (CREB) and Liver Kinase B1 (LKB-1), which induces PGC-1α to regulate mitochondria biogenesis (Than et al., 2011, Veeranki et al., 2011).
Cyclic Nucleotides
Enrique Pimentel in Handbook of Growth Factors, 2017
The manyfold physiologic effects of cAMP in eukaryotic cells are mediated exclusively through activation of the cAMP-dependent protein kinase (protein kinase A or A-kinase).49-53 The kinase holoenzyme is tetrameric and exists as an inactive complex of two regulatory (R) and two catalytic (C) subunits (R2C2). The R subunit contains two cAMP-binding sites, a dimer interaction site, and an autophosphorylation site. In addition, the holoenzyme contains interaction sites between the R and C subunits. Like most protein kinases, the function of the cAMP-dependent protein kinase depends on a regulatory mechanism and the enzyme is maintained in an inactive form in the absence of cAMP. When cAMP is generated by the action of hormones, growth factors, or other stimuli, it binds with a high affinity to the R subunit, and the complex dissociates to liberate active C subunits which appear to be identical. Under normal physiological conditions, this leads to dissociation of the holoenzyme into an R2-(cAMP)4 dimer and two catalytically active free C subunits. Crystal structure analysis of the C subunit at a resolution of 2.7 Å showed that the enzyme is bilobal with a deep cleft between the lobes.54 While the smaller lobe is associated with nucleotide binding, the larger lobe is primarily involved in peptide binding and catalysis.
Acquisition and Initiation of Sperm Motility
Claude Gagnon in Controls of Sperm Motility, 2020
It is well established that the protein kinase mediates the effect of cAMP in causing phosphorylation of specific proteins and alters the physiological response of the relevant cell. In sperm cells, although the presence of cAMP-dependent protein kinase and phosphoproteins has been suggested in many animal species (see Reference 28), their precise roles in sperm function remained obscure. We showed that both the initiation of motility in demembranated sperm and short-term phosphorylation of almost all phosphoproteins were inhibited by a protein kinase inhibitor from rabbit skeletal muscle,2 a specific A-kinase inhibitor such as H-8, H-9, and a corepeptide of a heat-stable A-kinase inhibitor.29 These results strongly imply the contribution of cAMP-dependent phosphorylation of a specific protein.
Ensifentrine (RPL554): an investigational PDE3/4 inhibitor for the treatment of COPD
Published in Expert Opinion on Investigational Drugs, 2019
Mario Cazzola, Luigino Calzetta, Paola Rogliani, Maria Gabriella Matera
The effect of ensifentrine on the function of cystic fibrosis transmembrane conductance regulator (CFTR), a membrane protein acting as an ion channel for the chloride ion and tightly regulated by the cAMP/protein kinase, a signaling pathway that is likely responsible for the prominent increase in ciliary beating, was studied in cell lines and primary human bronchial epithelial cells from cystic fibrosis patients carrying the Class IV R117H/F508del mutations [29]. Ensifentrine stimulated CFTR in the CF bronchial epithelial cell line under basal conditions in a dose-dependent manner by raising cAMP level adequately to activate CFTR. Additionally, it increased ciliary beating. It has suggested that these effects involve only PDE4 inhibition. There is also evidence that ensifentrine stimulates other Class III and Class IV mutants, in addition to R117H CFTR [30]. In fact, it markedly enhanced forskolin-stimulated CFTR-dependent short-circuit current activity in S549R and G551D-expressing cells respectively when administered alone or in combination with lumacaftor/ivacaftor.
Noncyclical and cyclical mastalgia in Turkish women: Prevalence, risk factors, health-care seeking and quality of life
Published in Health Care for Women International, 2022
Hacı Bolat, Özlem Aşcı, Servet Kocaöz, Semra Kocaöz
Methylxanthins in soft drinks, coffee, and chocolate may cause mastalgia by increasing cyclic adenosine monophosphate (cAMP). cAMP plays an important role in the stimulation of cellular proliferation through protein kinase production. This is thought to cause mammary fibrocystic changes that play a role in the etiology of mastalgia (Hafiz et al., 2018). Contradictory results have been reported in various studies (Eren et al., 2016; Koçoğlu et al., 2017; Mohammed, 2020; Russel, 1989). Avoiding foods containing methylxanthine for 8 weeks or more is reported to possibly reduce the symptoms and signs of mastalgia (Rosolowich, Saettler, Szuck, & Breast Disease Committee, 2006). We similarly found that consumption of caffeine, chocolate or soft drinks increased the likelihood of developing mastalgia.
Anti-melanogenic effects of extracellular vesicles derived from plant leaves and stems in mouse melanoma cells and human healthy skin
Published in Journal of Extracellular Vesicles, 2020
Ruri Lee, Hae Ju Ko, Kimin Kim, Yehjoo Sohn, Seo Yun Min, Jeong Ah Kim, Dokyun Na, Ju Hun Yeon
α-Melanocyte-stimulating hormone (α-MSH) binds to MC1R (melanocortin-1 receptor) on the cell surface and activates adenylate cyclase, which leads to an elevated level of intracellular cyclic AMP (cAMP). cAMP is mediated through cAMP-dependent protein kinase A which results in the phosphorylation of cAMP response element-binding protein (CREB). Activated CREB induces MITF, which is expressed in melanocytes and is known to play a critical role in the differentiation and development of melanocyte. MITF regulates tyrosinase-related protein (TRP) family, which are multienzyme complexes including tyrosinase (TYR), Tyrp1 (TRP1) and Dct (TRP2). TYR activity is more stable in the presence of TRP-1 and TRP-2, and TYR is coexpressed with TRP1 or TRP2 by the regulation of MITF in melanoma cells [25]. TRP1 is a necessary enzyme for the correct trafficking of TYR to melanin synthesis, and TRP2 plays an important role in TRP catalytic activity in the early stages in melanin synthesis. All three interact with one another in melanoma cells (Supplementary Figure S1) [26–31].
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