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https://www.readbyqxmd.com/read/28818614/the-transcription-of-atypical-protein-kinase-c-in-hemocytes-of-the-giant-freshwater-prawn-macrobrachium-rosenbergii-during-the-molt-stage-and-injection-of-pathogen-associated-compounds
#1
Yi-Chun Yeh, Chin-Chyuan Chang, Pai-Po Lee, Winton Cheng
Protein kinase C (PKC), which is involved in cell signaling pathways, comprises a family of serine/threonine kinases ubiquitously present in animals and its members are grouped on the basis of structural and activation characteristics into novel, classical, and atypical PKC forms. In this study, an atypical PKC of Macrobrachium rosenbergii, designated MraPKC, was successfully cloned, and its protein comprised structural domains similar to those of atypical PKC homologues, including the Phox and Bem1 (PB1) domain, a zinc finger phorbol-ester/DAG-type signature, protein kinase signatures, and a cAMP-dependent, cGMP-dependent, and PKC (AGC) kinase C-terminal domain...
August 14, 2017: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/28815720/pharmacological-evidence-of-involvement-of-nitric-oxide-pathway-in-anti-pruritic-effects-of-sumatriptan-in-chloroquine-induced-scratching-in-mice
#2
Nazgol-Sadat Haddadi, Sattar Ostadhadi, Saeed Shakiba, Khashayar Afshari, Nastaran Rahimi, Arash Foroutan, Ahmad-Reza Dehpour
Chloroquine (CQ) induces histamine-independent itch in human and mice. We recently reported the role of intradermal nitric oxide (NO)/ cyclic guanosine monophosphate (cGMP) pathway in CQ-evoked scratching in mice. Chloroquine stimulates neuronal nitric oxide synthase (nNOS) activity to over-producing NO in the skin. Sumatriptan, a 5-hydroxytryptamine 1b/1d receptors (5-HTR1b/1d) agonist, is involved in pain and used to treat migraine and cluster headaches. According to previous studies, sumatriptan inhibits NOS activity...
August 16, 2017: Fundamental & Clinical Pharmacology
https://www.readbyqxmd.com/read/28815566/maturation-promoting-factor-destabilization-mediates-human-chorionic-gonadotropin-induced-meiotic-resumption-in-rat-oocytes
#3
Meenakshi Tiwari, Shail K Chaube
Human chorionic gonadotropin (hCG) mimics the action of luteinizing hormone (LH) and triggers meiotic maturation and ovulation in mammals. The mechanism by which hCG triggers meiotic resumption in mammalian oocytes remains poorly understood. We aimed to find out the impact of hCG surge on morphological changes, adenosine 3',5'-cyclic monophosphate (cAMP), guanosine 3',5'-cyclic monophosphate (cGMP), cell division cycle 25B (Cdc25B), Wee1, early mitotic inhibitor 2 (Emi2), anaphase-promoting complex/cyclosome (APC/C), meiotic arrest deficient protein 2 (MAD2), phosphorylation status of cyclin-dependent kinase 1 (Cdk1), its activity and cyclin B1 expression levels during meiotic resumption from diplotene as well as metaphase-II (M-II) arrest in cumulus oocyte complexes (COCs)...
August 16, 2017: Development, Growth & Differentiation
https://www.readbyqxmd.com/read/28812418/neurotoxicity-of-cgmp-in-the-vertebrate-retina-from-the-initial-research-on-rd-mutant-mice-to-zebrafish-genetic-approaches
#4
Maria Iribarne, Ichiro Masai
Zebrafish are an excellent animal model for research on vertebrate development and human diseases. Sophisticated genetic tools including large-scale mutagenesis methodology make zebrafish useful for studying neuronal degenerative diseases. Here, we review zebrafish models of inherited ophthalmic diseases, focusing on cGMP metabolism in photoreceptors. cGMP is the second messenger of phototransduction, and abnormal cGMP levels are associated with photoreceptor death. cGMP concentration represents a balance between cGMP phosphodiesterase 6 (PDE6) and guanylate cyclase (GC) activities in photoreceptors...
August 16, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28810916/the-catsper-channel-and-its-roles-in-male-fertility-a-systematic-review
#5
REVIEW
Xiang-Hong Sun, Ying-Ying Zhu, Lin Wang, Hong-Ling Liu, Yong Ling, Zong-Li Li, Li-Bo Sun
The Catsper channel is a sperm-specific, Ca(2+)-permeable, pH-dependent, and low voltage-dependent channel that is essential for the hyperactivity of sperm flagellum, chemotaxis towards the egg, capacitation and acrosome reaction. All of these physiological events require calcium entry into sperm cells. Remarkably, Catsper genes are exclusively expressed in the testis during spermatogenesis, and are sensitive to ion channel-induced pH change, such as NHEs, Ca(2+)ATPase, K(+) channel, Hv1 channel and HCO3(-) transporters...
August 15, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28809932/rem-sleep-deprivation-induces-endothelial-dysfunction-and-hypertension-in-middle-aged-rats-roles-of-the-enos-no-cgmp-pathway-and-supplementation-with-l-arginine
#6
Jiaye Jiang, Zhongyuan Gan, Yuan Li, Wenqi Zhao, Hanqing Li, Jian-Pu Zheng, Yan Ke
Sleep loss can induce or aggravate the development of cardiovascular and cerebrovascular diseases. However, the molecular mechanism underlying this phenomenon is poorly understood. The present study was designed to investigate the effects of REM sleep deprivation on blood pressure in rats and the underlying mechanisms of these effects. After Sprague-Dawley rats were subjected to REM sleep deprivation for 5 days, their blood pressures and endothelial function were measured. In addition, one group of rats was given continuous access to L-arginine supplementation (2% in distilled water) for the 5 days before and the 5 days of REM sleep deprivation to reverse sleep deprivation-induced pathological changes...
2017: PloS One
https://www.readbyqxmd.com/read/28808570/nitric-oxide-cyclic-gmp-pathway-mediates-the-endothelin-1-upregulation-of-adiponectin-expression-in-rat-cardiomyocytes
#7
Bingyan Guo, Yongjun Li, Xin Jin, Suyun Liu, Chenglong Miao
Endothelin-1 (ET-1) serves an important role in the development of cardiac dysfunction and heart failure. ET-1 and angiotensin II (AngII) comprise a mutually reciprocal signalling network in the myocardium and serve similar or additive roles in the development of heart failure. Our previous study previously demonstrated that AngII upregulated the expression of APN in cardiomyocytes through an AngII receptor type 2/nitric oxide (NO)/cyclic GMP(cGMP)-dependent pathway. The purpose of the present study was to determine the effects of ET-1 and the additive effects of ET-1 and AngII on the gene expression and secretion of APN, and the underlying mechanisms involved...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28808213/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#8
Kevin Lee, Gary A Piazza
The activation of the Wnt/β-catenin signaling cascade has been well studied and documented in colorectal cancer (CRC). The long-term use of non-steroidal anti-inflammatory drugs (NSAIDs) has been shown to reduce the incidence and risk of death from CRC in numerous epidemiological studies. The NSAID sulindac has also been reported to cause regression of precancerous adenomas in individuals with familial adenomatous polyposis who are at high risk of developing CRC. The mechanism responsible for cancer chemopreventive activity of NSAIDs is not well understood but may be unrelated to their cyclooxygenase inhibitory activity...
January 19, 2017: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807144/regulation-of-l-type-cav1-3-channel-activity-and-insulin-secretion-by-the-cgmp-pkg-signaling-pathway
#9
Alejandro Sandoval, Paz Duran, María A Gandini, Arturo Andrade, Angélica Almanza, Simon Kaja, Ricardo Felix
cGMP is a second messenger widely used in the nervous system and other tissues. One of the major effectors for cGMP is the serine/threonine protein kinase, cGMP-dependent protein kinase (PKG), which catalyzes the phosphorylation of a variety of proteins including ion channels. Previously, it has been shown that the cGMP-PKG signaling pathway inhibits Ca(2+) currents in rat vestibular hair cells and chromaffin cells. This current allegedly flow through voltage-gated CaV1.3L-type Ca(2+) channels, and is important for controlling vestibular hair cell sensory function and catecholamine secretion, respectively...
September 2017: Cell Calcium
https://www.readbyqxmd.com/read/28806854/generation-of-xeno-free-cgmp-compliant-patient-specific-ipscs-from-skin-biopsy
#10
Luke A Wiley, Kristin R Anfinson, Cathryn M Cranston, Emily E Kaalberg, Malia M Collins, Robert F Mullins, Edwin M Stone, Budd A Tucker
This unit describes protocols for the generation of clinical-grade patient-specific induced pluripotent stem cell (iPSC)-derived retinal cells from patients with inherited retinal degenerative blindness. Specifically, we describe how, using xeno-free reagents in an ISO class 5 environment, one can isolate and culture dermal fibroblasts, generate iPSCs, and derive autologous retinal cells via 3-D differentiation. The universal methods described herein for the isolation of dermal fibroblasts and generation of iPSCs can be employed regardless of disease, tissue, or cell type of interest...
August 14, 2017: Current Protocols in Stem Cell Biology
https://www.readbyqxmd.com/read/28796496/discovery-of-clinical-candidate-n-1s-1-3-fluoro-4-trifluoromethoxy-phenyl-2-methoxyethyl-7-methoxy-2-oxo-2-3-dihydropyrido-2-3-b-pyrazine-4-1h-carboxamide-tak-915-a-highly-potent-selective-and-brain-penetrating-phosphodiesterase-2a-inhibitor-for-the-treatment
#11
Satoshi Mikami, Shinji Nakamura, Tomoko Ashizawa, Izumi Nomura, Masanori Kawasaki, Shigekazu Sasaki, Hideyuki Oki, Hironori Kokubo, Isaac D Hoffman, Hua Zou, Noriko Uchiyama, Kosuke Nakashima, Naomi Kamiguchi, Haruka Imada, Noriko Suzuki, Hiroki Iwashita, Takahiko Taniguchi
Phosphodiesterase (PDE) 2A inhibitors have emerged as a novel mechanism with potential therapeutic option to ameliorate cognitive dysfunction in schizophrenia or Alzheimer's disease through upregulation of cyclic nucleotides in the brain, and thereby achieve potentiation of cyclic nucleotide signaling pathways. This article details the expedited optimization of our recently disclosed pyrazolo[1,5-a]pyrimidine lead compound 4b, leading to the discovery of clinical candidate 36 (TAK-915), which demonstrates an appropriate combination of potency, PDE selectivity, and favorable pharmacokinetic (PK) properties, including brain penetration...
August 10, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28796407/effects-of-gene-knockdown-of-cnp-on-ventricular-remodeling-after-myocardial-ischemia-reperfusion-injury-through-nprb-cgmp-signaling-pathway-in-rats
#12
Lian-He Wu, Qi Zhang, Shen Zhang, Lu-Yu Meng, Yan-Chi Wang, Cun-Jian Sheng
This study aimed to explore effects of CNP on ventricular remodeling following myocardial ischemia-reperfusion (I/R) injury through the NPRB/cGMP signaling pathway. Rat cardiomyocyteswere assigned into: control, I/R, I/R + CNP, and I/R+ 8-Br-cGMP groups. ELISA, qRT-PCR and western blotting were used to detect cGMP content and expression, respectively. After model establishment of I/R rats, normal control, CNP(-/-) control, I/R, and CNP(-/-) groups were set. Indexes of heart were detected using echocardiography and hemodynamics...
August 10, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28793191/structural-basis-of-analog-specificity-in-pkg-i-and-ii
#13
James C Campbell, Philipp Henning, Eugen Franz, Banumathi Sankaran, Friedrich W Herberg, Choel Kim
Cyclic GMP analogs, 8-Br, 8-pCPT, and PET-cGMP, have been widely used for characterizing cellular functions of cGMP dependent protein kinase (PKG) I and II isotypes. However, interpreting results obtained using these analogs has been difficult due to their low isotype specificity. Additionally each isotype has two binding sites with different cGMP affinities and analog selectivities, making understanding the molecular basis for isotype specificity of these compounds even more challenging. To determine isotype specificity of cGMP analogs and their structural basis, we generated the full-length regulatory domains of PKG I and II isotypes with each binding site disabled, determined their affinities for these analogs, and obtain co-crystal structures of both isotypes bound with cGMP analogs...
August 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28793049/possible-mechanisms-involved-in-the-vasorelaxant-effect-produced-by-clobenzorex-in-aortic-segments-of-rats
#14
J Lozano-Cuenca, A González-Hernández, O A López-Canales, J R Villagrana-Zesati, J D Rodríguez-Choreão, R Morín-Zaragoza, E F Castillo-Henkel, J S López-Canales
Clobenzorex is a metabolic precursor of amphetamine indicated for the treatment of obesity. Amphetamines have been involved with cardiovascular side effects such as hypertension and pulmonary arterial hypertension. The aim of the present study was to investigate whether the direct application of 10-9-10-5 M clobenzorex on isolated phenylephrine-precontracted rat aortic rings produces vascular effects, and if so, what mechanisms may be involved. Clobenzorex produced an immediate concentration-dependent vasorelaxant effect at the higher concentrations (10-7...
August 7, 2017: Brazilian Journal of Medical and Biological Research, Revista Brasileira de Pesquisas Médicas e Biológicas
https://www.readbyqxmd.com/read/28792962/aberrant-cgmp-signaling-persists-during-recovery-in-mice-with-oxygen-induced-pulmonary-hypertension
#15
Marta Perez, Keng Jin Lee, Herminio J Cardona, Joann M Taylor, Mary E Robbins, Gregory B Waypa, Sara K Berkelhamer, Kathryn N Farrow
Bronchopulmonary dysplasia (BPD), a common complication of preterm birth, is associated with pulmonary hypertension (PH) in 25% of infants with moderate to severe BPD. Neonatal mice exposed to hyperoxia for 14d develop lung disease similar to BPD, with evidence of associated PH. The cyclic guanosine monophosphate (cGMP) signaling pathway has not been well studied in BPD-associated PH. In addition, there is little data about the natural history of hyperoxia-induced PH in mice or the utility of phosphodiesterase-5 (PDE5) inhibition in established disease...
2017: PloS One
https://www.readbyqxmd.com/read/28789837/investigating-the-amyloid-beta-enhancing-effect-of-cgmp-in-neuro2a-cells
#16
Elisa Calcagno, Francesca Caudano, Mario Passalacqua, Maria A Pronzato, Ernesto Fedele, Roberta Ricciarelli
Long-term potentiation (LTP) and the process of memory formation require activation of cyclic guanosine monophosphate (cGMP) and cyclic adenosine monophosphate (cAMP) pathways. Notably, recent evidence indicated that both cyclic nucleotides boost the production of amyloid-beta (Aβ) peptides. In particular, cAMP was shown to favor hippocampal LTP by stimulating the synthesis of the amyloid precursor protein APP, whereas cGMP was found to enhance LTP and to improve memory by increasing Aβ levels without affecting the expression of APP...
August 5, 2017: Mechanisms of Ageing and Development
https://www.readbyqxmd.com/read/28783422/the-role-of-nitric-oxide-in-the-intraocular-pressure-lowering-efficacy-of-latanoprostene-bunod-review-of-nonclinical-studies
#17
Megan E Cavet, Heleen H DeCory
Latanoprostene bunod (LBN) is a topical ophthalmic therapeutic for the reduction of intraocular pressure (IOP) in patients with open-angle glaucoma or ocular hypertension (OHT). LBN is composed of latanoprost acid (LA) linked to a nitric oxide (NO)-donating moiety and is the first NO-releasing prostaglandin analog to be submitted for marketing authorization in the United States. The role of latanoprost in increasing uveoscleral outflow of aqueous humor (AqH) is well established. Herein, we review findings from nonclinical studies, which evaluated the role of NO in the IOP-lowering efficacy of LBN...
August 7, 2017: Journal of Ocular Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28782641/nitric-oxide-cgmp-signaling-via-guanylyl-cyclase-isoform-1-modulates-glutamate-and-gaba-release-in-somatosensory-cortex-of-mice
#18
Qi Wang, Evanthia Mergia, Doris Koesling, Thomas Mittmann
In hippocampus, two guanylyl cyclases (NO-GC1 and NO-GC2) are involved in the transduction of the effects of nitric oxide (NO) on synaptic transmission. However, the respective roles of the NO-GC isoforms on synaptic transmission are less clear in other regions of the brain. In the present study, we used knock-out mice deficient for the NO-GC1 isoform (NO-GC1 KO) to analyze its role in the glutamatergic and GABAergic neurotransmission at pyramidal neurons in layers II/III of somatosensory cortex. NO-GC1 KO slices revealed reduced frequencies of miniature excitatory- and inhibitory-postsynaptic currents, increased paired-pulse ratios and decreased input-output curves of evoked signals, which indicated the reduction of glutamate and GABA release in NO-GC1 KO mice...
August 4, 2017: Neuroscience
https://www.readbyqxmd.com/read/28780894/gene-therapy-for-hypertension
#19
Ludovit Paulis, Heinrich Franke, Fedor Simko
The control of hypertension and the resulting cardiovascular events is still insufficient. Thus, the search for novel means for blood pressure (BP) reduction remains worth further clinical and research attention. The advances in vector and construct design sketch the use of gene therapy in hypertension. Areas covered: The authors have searched for studies using gene therapy in hypertension reporting BP outcomes. They have identified 63 experimental studies demonstrating feasible targeting of the classical and new renin-angiotensin-aldosterone system, β1-adrenergic receptor, NO-cGMP axis, endothelin, natriuretic peptides, kallikrein system, cytochrome P-450 hydroxylase, oncogenes, growth factors, interleukins, angiopoietin-1, adrenomedullin or Klotho in small rodents...
August 7, 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#20
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
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