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https://www.readbyqxmd.com/read/28630469/c2238-anp-gene-variant-promotes-increased-platelet-aggregation-through-the-activation-of-nox2-and-the-reduction-of-camp
#1
Roberto Carnevale, Pasquale Pignatelli, Giacomo Frati, Cristina Nocella, Rosita Stanzione, Daniele Pastori, Simona Marchitti, Valentina Valenti, Maria Santulli, Emanuele Barbato, Teresa Strisciuglio, Leonardo Schirone, Carmine Vecchione, Francesco Violi, Massimo Volpe, Speranza Rubattu, Sebastiano Sciarretta
Subjects carrying the C2238 variant of the atrial natriuretic peptide (ANP) gene have a higher occurrence of stroke and acute coronary syndrome, suggesting an increased predisposition to acute thrombotic events in these subjects. We evaluated for the first time the direct effects of mutant ANP (C2238/αANP) on platelet activation in vitro and in human subjects. In vitro, platelets were incubated with no peptide, with T2238/αANP (WT) or with C2238/αANP at different concentrations. C2238/αANP (10(-10) M) induced higher collagen-induced platelet aggregation with respect to both control without ANP and T2238/αANP...
June 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28629760/cardiac-overexpression-of-epac1-in-transgenic-mice-rescues-lipopolysaccharide-induced-cardiac-dysfunction-and-inhibits-jak-stat-pathway
#2
Huiling Jin, Takayuki Fujita, Meihua Jin, Reiko Kurotani, Iyuki Namekata, Shogo Hamaguchi, Yuko Hidaka, Wenqian Cai, Kenji Suita, Yoshiki Ohnuki, Yasumasa Mototani, Kouichi Shiozawa, Rajesh Prajapati, Chen Liang, Masanari Umemura, Utako Yokoyama, Motohiko Sato, Hikaru Tanaka, Satoshi Okumura, Yoshihiro Ishikawa
Pro-inflammatory cytokines are released in septic shock and impair cardiac function via the Jak-STAT pathway. It is well known that sympathetic stimulation leads to coupling of the β-adrenergic receptor/Gs/adenylyl cyclase, a membrane-bound enzyme that catalyzes the conversion of ATP to cAMP, thereby stimulating protein kinase A (PKA) and ultimately compensating for cardiac dysfunction. The mechanism of such compensation by catecholamine has been traditionally understood as PKA-mediated enforcement of cardiac contractility...
June 16, 2017: Journal of Molecular and Cellular Cardiology
https://www.readbyqxmd.com/read/28627700/isolation-of-rat-schwann-cells-based-on-cell-sorting
#3
Mi Shen, Wei Tang, Zheng Cao, Xuemin Cao, Fei Ding
The present study presented a protocol that can be used to obtain rapidly a high purity of proliferating rat Schwann cells from freshly dissociated rat peripheral nerves. The sciatic nerves of newborn rats (1‑3 day old) were dissociated, and the Schwann cells (SCs) were purified using fluorescence‑activated cell sorting (FACS) based on the SC membrane‑specific expression of the low‑affinity nerve growth factor receptor, p75NGFR and oligodendrocyte marker 4. Following sorting, the cells were plated on poly‑l‑lysine‑coated dishes in SC culture medium containing DMEM with 10% FBS, 1% penicillin/streptomycin, 2 µM forskolin and 10 ng/ml HRG...
June 14, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28627372/regulatory-role-of-melatonin-and-bmp-4-in-prolactin-production-by-rat-pituitary-lactotrope-gh3-cells
#4
Kanako Ogura-Ochi, Satoshi Fujisawa, Nahoko Iwata, Motoshi Komatsubara, Yuki Nishiyama, Naoko Tsukamoto-Yamauchi, Kenichi Inagaki, Jun Wada, Fumio Otsuka
The effects of melatonin on prolactin production and its regulatory mechanism remain uncertain. We investigated the regulatory role of melatonin in prolactin production using rat pituitary lactotrope GH3 cells by focusing on the bone morphogenetic protein (BMP) system. Melatonin receptor activation, induced by melatonin and its receptor agonist ramelteon, significantly suppressed basal and forskolin-induced prolactin secretion and prolactin mRNA expression in GH3 cells. The melatonin MT2 receptor was predominantly expressed in GH3 cells, and the inhibitory effects of melatonin on prolactin production were reversed by treatment with the receptor antagonist luzindole, suggesting functional involvement of MT2 action in the suppression of prolactin release...
June 13, 2017: Peptides
https://www.readbyqxmd.com/read/28623279/divergent-regulation-of-actin-dynamics-and-megakaryoblastic-leukemia-1-and-2-mkl1-2-by-camp-in-endothelial-and-smooth-muscle-cells
#5
Madeleine C Smith, Claire A Hudson, Tomomi E Kimura, Stephen J White, Graciela B Sala-Newby, Andrew C Newby, Mark Bond
Proliferation and migration of vascular smooth muscle cells (VSMCs) or endothelial cell (ECs) promote or inhibit, respectively, restenosis after angioplasty, vein graft intimal thickening and atherogenesis. Here we investigated the effects of cAMP-induced cytoskeletal remodelling on the serum response factor (SRF) co-factors Megakaryoblastic Leukemia-1 and -2 (MKL1 and MKL2) and their role in controlling VSMC and EC proliferation and migration. Elevation of cAMP using forskolin, dibutyryl-cAMP (db-cAMP), BAY60-6583 or Cicaprost induced rapid cytoskeleton remodelling and inhibited proliferation and migration in VSMCs but not EC...
June 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28623133/prostaglandin-d2-enhances-lipid-accumulation-through-suppression-of-lipolysis-via-dp2-crth2-receptors-in-adipocytes
#6
Eri Wakai, Kosuke Aritake, Yoshihiro Urade, Ko Fujimori
Prostaglandin (PG) D2 enhanced lipid accumulation in adipocytes. However, its molecular mechanismremains unclear. In this study, we investigated the regulatory mechanisms of PGD2-elevated lipid accumulation in mouse adipocytic 3T3-L1 cells. The Gi-coupled DP2 (CRTH2) receptors (DP2R), one of the two-types of PGD2 receptors were dominantly expressed in adipocytes. A DP2R antagonist, CAY10595, but not DP1 receptor antagonist, BWA868C cleared the PGD2-elevated intracellular triglyceride level. While, a DP2R agonist, 15R-15-methyl PGD2 (15R) increased the mRNA levels of the adipogenic and lipogenic genes, and decreased the glycerol release level...
June 13, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28615646/hydrogen-sulfide-stimulates-cftr-in-xenopus-oocytes-by-activation-of-the-camp-pka-signalling-axis
#7
Alexander Perniss, Kathrin Preiss, Marcel Nier, Mike Althaus
Hydrogen sulfide (H2S) has been recognized as a signalling molecule which affects the activity of ion channels and transporters in epithelial cells. The cystic fibrosis transmembrane conductance regulator (CFTR) is an epithelial anion channel and a key regulator of electrolyte and fluid homeostasis. In this study, we investigated the regulation of CFTR by H2S. Human CFTR was heterologously expressed in Xenopus oocytes and its activity was electrophysiologically measured by microelectrode recordings. The H2S-forming sulphur salt Na2S as well as the slow-releasing H2S-liberating compound GYY4137 increased transmembrane currents of CFTR-expressing oocytes...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28614607/anatomical-and-functional-implications-of-crh-neurons-in-a-septal-nucleus-of-the-avian-brain-an-emphasis-on-glial-neuronal-interaction-via-v1a-receptors-in-vitro
#8
Gurueswar Nagarajan, Alexander Jurkevich, Seong W Kang, Wayne J Kuenzel
Previously, we showed that corticotropin releasing hormone immunoreactive (CRH-ir) neurons in a septal structure are associated with stress and the hypothalamo-pituitary-adrenal axis in birds. In this study, we focused upon CRH-ir neurons located within the septal structure called the nucleus of the hippocampal commissure (NHpC). Immunocytochemical and gene expression analyses were used to identify the anatomical and functional characteristics of cells within the NHpC. A comparative morphometry analysis showed that CRH-ir neurons in the NHpC were significantly larger than CRH-ir parvocellular neurons in the paraventricular nucleus of the hypothalamus (PVN) and lateral bed nucleus of the stria terminalis...
June 14, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/28611079/elevated-camp-improves-signal-to-noise-ratio-in-amphibian-rod-photoreceptors
#9
Luba A Astakhova, Darya A Nikolaeva, Tamara V Fedotkina, Victor I Govardovskii, Michael L Firsov
The absolute sensitivity of vertebrate retinas is set by a background noise, called dark noise, which originates from several different cell types and is generated by different molecular mechanisms. The major share of dark noise is produced by photoreceptors and consists of two components, discrete and continuous. Discrete noise is generated by spontaneous thermal activations of visual pigment. These events are undistinguishable from real single-photon responses (SPRs) and might be considered an equivalent of the signal...
June 13, 2017: Journal of General Physiology
https://www.readbyqxmd.com/read/28609289/adverse-eff-ects-of-polymeric-nanoparticle-poly-ethylene-glycol-block-polylactide-methyl-ether-peg-b-pla-on-steroid-hormone-secretion-by-porcine-granulosa-cells
#10
Sona Scsukova, Mlynarcikova A Bujnakova, A Kiss, E Rollerova
OBJECTIVES: Development of nanoparticles (NPs) for biomedical applications, including medical imaging and drug delivery, is currently undergoing a dramatic expansion. Diverse effects of different type NPs relating to mammalian reproductive tissues have been demonstrated. Th e objective of this study was to explore the in vitro effects of polymeric nanoparticle poly(ethylene glycol)-blockpolylactide methyl ether (PEG-b-PLA NPs) on functional state and viability of ovarian granulosa cells (GCs), which play an important role in maintaining ovarian function and female fertility...
April 25, 2017: Endocrine Regulations
https://www.readbyqxmd.com/read/28603838/compartmentalized-camp-responses-to-prostaglandin-ep2-receptor-activation-in-human-airway-smooth-muscle-cells
#11
Shailesh R Agarwal, Kathryn Miyashiro, Htun Latt, Rennolds S Ostrom, Robert D Harvey
BACKGROUND AND PURPOSE: Previous studies indicate that prostaglandin EP2 receptors (EP2 Rs) selectively couple to adenylyl cyclase type 2 (AC2) in non-lipid raft domains of airway smooth muscle (ASM) cells, where they regulate specific cAMP-dependent responses. The goal of the present study was to identify the cellular microdomains where EP2 Rs stimulate cAMP production. EXPERIMENTAL APPROACH: FRET-based cAMP biosensors were targeted to different subcellular locations of primary human ASM cells...
June 11, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28603044/relaxation-of-isolated-guinea-pig-trachea-by-apigenin-a-constituent-of-celery-via-inhibition-of-phosphodiesterase
#12
Junn-Lain Chen, Wun-Chang Ko
Apigenin, was reported to have vasodilatory effects by inhibiting Ca(2+) influx through both voltage- and receptor-operated calcium channels, but not by inhibiting cAMP- or cGMP-phosphodiesterases (PDEs) in rat thoracic aorta. However, apigenin was reported to inhibit PDE1, 2 and 3 in guinea-pig lung and heart. The aim of this study was to clarify that guinea-pig tracheal relaxation by apigenin whether via PDE inhibition. We isometrically recorded the tension of isolated guinea-pig tracheal segments on a polygraph...
June 9, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28603032/%C3%AE-2-adrenergic-receptor-mediated-in-vitro-regulation-of-human-hepatic-drug-transporter-expression-by-epinephrine
#13
Abdullah Mayati, Amélie Moreau, Claire Denizot, Bruno Stieger, Yannick Parmentier, Olivier Fardel
The catecholamine epinephrine is known to repress expression of hepatic drug metabolizing enzymes such as cytochromes P-450. The present study was designed to determine whether epinephrine may also target expression of main hepatic drug transporters, that play a major role in liver detoxification and are commonly coordinately regulated with drug detoxifying enzymes. Treatment of primary human hepatocytes with 10μM epinephrine for 24h repressed mRNA expression of various transporters, such as the sinusoidal influx transporters NTCP, OATP1B1, OATP2B1, OAT2, OAT7 and OCT1 and the efflux transporters MRP2, MRP3 and BSEP, whereas it induced that of MDR1, but failed to alter that of BCRP...
June 8, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28602959/butyric-acid-regulates-progesterone-and-estradiol-secretion-via-camp-signaling-pathway-in-porcine-granulosa-cells
#14
Naisheng Lu, Mengjiao Li, Hulong Lei, Xueyuan Jiang, Weilong Tu, Yang Lu, Dong Xia
Butyric acid (BA), one of the short chain fatty acids (SCFAs), has positive actions on the metabolism, inflammation, etc. However, whether it influences the reproductive physiology and if so the detail mechanism involved has not yet been determined. In this study, the porcine granulosa cells (PGCs) were treated with gradient concentrations of BA. After 24h culture, 0.05mM BA significantly stimulated the progesterone (P4) secretion (P<0.05), 5mM and 10mM BA significantly inhibited the P4 secretion (P<0...
June 8, 2017: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/28597607/immaturity-of-insulin-secretion-by-pancreatic-islets-isolated-from-one-human-neonate
#15
Jean-Claude Henquin, Myriam Nenquin
Human β-cells are functionally mature by the age of one year. The timing and mechanisms of this maturation are unknown owing to the exceptional availability of testable tissue. Here, we report the first in vitro study of insulin secretion by islets from a 5 day-old newborn. Glucose alone was inefficient but glucose-stimulation became concentration-dependent, displayed a biphasic time-course and was of similar magnitude as in infant islets when β-cell cAMP was raised by forskolin. Tolbutamide alone was effective in low glucose, but its effect was not augmented by high glucose...
June 8, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28596237/the-snare-protein-syntaxin1a-plays-an-essential-role-in-biphasic-exocytosis-of-the-incretin-hormone-glucagon-like-peptide-1
#16
Sarah E Wheeler, Holly M Stacey, Yasaman Nahaei, Stephen J Hale, Alexandre B Hardy, Frank Reimann, Fiona M Gribble, Pierre Larraufie, Herbert Y Gaisano, Patricia L Brubaker
Exocytosis of the hormone, glucagon-like peptide-1 (GLP-1), by the intestinal L-cell is essential for the incretin effect after nutrient ingestion, and is critical for the actions of dipeptidylpeptidase IV inhibitors that enhance GLP-1 levels in patients with type 2 diabetes. 2-Photon microscopy revealed that exocytosis of GLP-1 is biphasic, with a 1(st) peak at 1-6min and a 2(nd) peak at 7-12min after stimulation with forskolin. Approximately 75% of the exocytotic events were represented by compound granule fusion, and the remainder were accounted for by full fusion of single granules, under basal and stimulated conditions...
June 8, 2017: Diabetes
https://www.readbyqxmd.com/read/28592822/bacterial-sphingomyelinase-is-a-state-dependent-inhibitor-of-the-cystic-fibrosis-transmembrane-conductance-regulator-cftr
#17
B B Stauffer, G Cui, K A Cottrill, D T Infield, N A McCarty
Sphingomyelinase C (SMase) inhibits CFTR chloride channel activity in multiple cell systems, an effect that could exacerbate disease in CF and COPD patients. The mechanism by which sphingomyelin catalysis inhibits CFTR is not known but evidence suggests that it occurs independently of CFTR's regulatory "R" domain. In this study we utilized the Xenopus oocyte expression system to shed light on how CFTR channel activity is reduced by SMase. We found that the pathway leading to inhibition is not membrane delimited and that inhibited CFTR channels remain at the cell membrane, indicative of a novel silencing mechanism...
June 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28592413/recruitment-of-endosomal-signaling-mediates-the-forskolin-modulation-of-guinea-pig-cardiac-neuron-excitability
#18
Jean C Hardwick, Todd A Clason, John D Tompkins, Beatrice M Girard, Caitlin N Baran, Laura A Merriam, Victor May, Rodney L Parsons
Forskolin, a selective activator of adenylyl cyclase (AC), commonly is used to establish actions of G protein coupled receptors (GPCRs) that are initiated primarily through activation of AC/cAMP signaling pathways. In the present study, forskolin was used to evaluate the potential role of AC/cAMP, which is a major signaling mechanism for the pituitary adenylate cyclase-activating polypeptide (PACAP)-selective PAC1 receptor, in the regulation of guinea pig cardiac neuronal excitability. Forskolin (5-10 µM) increases excitability in ~60 % of the cardiac neurons...
June 7, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/28588484/akrinor-tm-a-cafedrine-theodrenaline-mixture-20-1-increases-force-of-contraction-of-human-atrial-myocardium-but-does-not-constrict-internal-mammary-artery-in-vitro
#19
Benjamin Kloth, Simon Pecha, Eileen Moritz, Yvonne Schneeberger, Klaus-Dieter Söhren, Edzard Schwedhelm, Hermann Reichenspurner, Thomas Eschenhagen, Rainer H Böger, Torsten Christ, Sebastian N Stehr
Background: Intraoperative hypotension is a common problem and direct or indirect sympathomimetic drugs are frequently needed to stabilize blood pressure. Akrinor(TM) consists of the direct and the indirect sympathomimetic noradrenaline and norephedrine. Both substances are covalently bound to the phosphodiesterase (PDE) inhibitor theophylline, yielding theodrenaline and cafedrine, respectively. We investigated pharmacodynamic effects of Akrinor(TM) and its constituents on contractile force and tension in human atrial trabeculae and internal A...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28581524/smurf1-regulates-lung-cancer-cell-growth-and-migration-through-interaction-with-and-ubiquitination-of-pipki%C3%AE
#20
H Li, N Xiao, Y Wang, R Wang, Y Chen, W Pan, D Liu, S Li, J Sun, K Zhang, Y Sun, X Ge
Type Iγ phosphatidylinositol phosphate kinase (PIPKIγ), a phospholipid kinase generating PIP2, is positively expressed in breast cancer tissues, which correlates intimately with the progression of patients. However, little is known about the expression level of PIPKIγ in patients with other cancer types as well as their underlying regulation mechanisms. Here, we report that PIPKIγ is highly expressed in lung cancer tissues and its expression level is critical for lung cancer cell proliferation, which may serve as a prognostic marker for lung cancer patients...
June 5, 2017: Oncogene
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