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https://www.readbyqxmd.com/read/29030485/crosstalk-between-pka-and-pkg-controls-ph-dependent-host-cell-egress-of-toxoplasma-gondii
#1
Yonggen Jia, Jean-Baptiste Marq, Hugo Bisio, Damien Jacot, Christina Mueller, Lu Yu, Jyoti Choudhary, Mathieu Brochet, Dominique Soldati-Favre
Toxoplasma gondii encodes three protein kinase A catalytic (PKAc1-3) and one regulatory (PKAr) subunits to integrate cAMP-dependent signals. Here, we show that inactive PKAc1 is maintained at the parasite pellicle by interacting with acylated PKAr. Either a conditional knockdown of PKAr or the overexpression of PKAc1 blocks parasite division. Conversely, down-regulation of PKAc1 or stabilisation of a dominant-negative PKAr isoform that does not bind cAMP triggers premature parasite egress from infected cells followed by serial invasion attempts leading to host cell lysis...
October 13, 2017: EMBO Journal
https://www.readbyqxmd.com/read/29028532/new-dimeric-cgmp-analogues-reduce-proliferation-in-three-colon-cancer-cell-lines
#2
Dorit Hoffmann, Andreas Rentsch, Eleonora Vighi, Evelina Bertolotti, Antonella Comitato, Frank Schwede, Hans-Gottfried Genieser, Valeria Marigo
Activation of the cGMP-dependent protein kinase G (PKG) can inhibit growth and/or induce apoptosis in colon cancer. In this study we evaluated the effects on cell viability, cell death and proliferation of novel dimeric cGMP analogues, compared to a monomeric compound. Three colon cancer cell lines, which only express isoform 2 of PKG, were treated with these novel cGMP analogues and responded with increased PKG activity. cGMP analogues reduced cell viability in the three cell lines and this was due to a cytostatic rather than cytotoxic effect...
September 27, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29024896/identification-of-a-soluble-guanylate-cyclase-in-rbcs-preserved-activity-in-patients-with-coronary-artery-disease
#3
Miriam M Cortese-Krott, Evanthia Mergia, Christian M Kramer, Wiebke Lückstädt, Jiangning Yang, Georg Wolff, Christina Panknin, Thilo Bracht, Barbara Sitek, John Pernow, Johannes-Peter Stasch, Martin Feelisch, Doris Koesling, Malte Kelm
Endothelial dysfunction is associated with decreased NO bioavailability and impaired activation of the NO receptor soluble guanylate cyclase (sGC) in the vasculature and in platelets. Red blood cells (RBCs) are known to produce NO under hypoxic and normoxic conditions; however evidence of expression and/or activity of sGC and downstream signaling pathway including phopshodiesterase (PDE)-5 and protein kinase G (PKG) in RBCs is still controversial. In the present study, we aimed to investigate whether RBCs carry a functional sGC signaling pathway and to address whether this pathway is compromised in coronary artery disease (CAD)...
September 8, 2017: Redox Biology
https://www.readbyqxmd.com/read/29021382/sustained-activation-of-guanylate-cyclase-a-with-tdt-a-natriuretic-peptide-derivative-exhibits-cardiorenal-protection-in-dahl-salt-sensitive-hypertensive-rats
#4
Shohei Oishi, Naoko Suzuki, Yuri Hasui, Tsuyoshi Homma, Masanori Obana, Takahiro Nagayama, Yasushi Fujio
Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive rats (DS rats). Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared to native human atrial NP (hANP)...
October 11, 2017: Journal of Pharmacology and Experimental Therapeutics
https://www.readbyqxmd.com/read/29016749/differential-enos-signalling-by-platelet-subpopulations-regulates-adhesion-and-aggregation
#5
Aneta Radziwon-Balicka, Gabriela Lesyk, Valentina Back, Teresa Fong, Erica L Loredo-Calderon, Bin Dong, Haitham El-Sikhry, Ahmed A El-Sherbani, Ayman El-Kadi, Stephen Ogg, Arno Siraki, John M Seubert, Maria Jose Santos-Martinez, Marek W Radomski, Carlos A Velazquez-Martinez, Ian R Winship, Paul Jurasz
Aims: In addition to maintaining hemostasis, circulating blood platelets are the cellular culprits that form occlusive thrombi in arteries and veins. Compared to blood leukocytes, which exist as functionally distinct subtypes, platelets are considered to be relatively simple cell fragments that form vascular system plugs without a differentially regulated cellular response. Hence, investigation into platelet subpopulations with distinct functional roles in hemostasis/thrombosis has been limited...
September 4, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28990076/global-transcriptome%C3%A2-wide-analysis-of-the-function-of-gddr-in-acute-gastric-lesions
#6
Ziqiang Zhang, Jie Zhu, Yuanqiang Dong, Hongyuan Xu, Tao Jiang, Wenshuai Li, Diannan Xu, Liubin Shi, Jianghong Yu, Jun Zhang, Jianjun Du
Acute gastric lesions induced by stress are frequent occurrences in medical establishments. The gastric dramatic downrelated gene (GDDR) is a secreted protein, which is abundantly expressed in normal gastric epithelia and is significantly decreased in gastric cancer. In our previous study, it was found that GDDR aggravated stress‑induced acute gastric lesions. However, the role of GDDR in acute gastric lesions remains to be fully elucidated. In the present study, RNA sequencing was performed in order to examine the gene expression profile regulated by GDDR in acute gastric lesions...
October 2, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28973370/genetic-deletion-of-the-nos3-gene-in-cav1-mice-restores-aqueous-humor-outflow-function
#7
Maomao Song, Jihong Wu, Yuan Lei, Xinghuai Sun
Purpose: The purpose of this study was to investigate the impact of genetic deletion of NOS3 in CAV1-/- mice on aqueous humor outflow function using a mouse genetic double knockout model (DKO, NOS3-/- CAV1-/-). Methods: IOP was measured in DKO, NOS3 KO, CAV1 KO, and wild-type (WT) mice by rebound tonometry. Outflow facility was measured by perfusing enucleated mouse eyes at multiple pressure steps. Sodium nitroprusside (SNP) and L-NG-nitroarginine methyl ester (L-NAME) was administered topically, whereas the contralateral eyes served as vehicle controls...
October 1, 2017: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/28957808/regulation-of-intracellular-calcium-by-carbon-monoxide-in-human-bronchial-epithelial-cells
#8
Rui-Gang Zhang, Chung-Yin Yip, Wing-Hung Ko
BACKGROUND/AIMS: Carbon monoxide (CO) is an important autocrine/paracrine messenger involved in a variety of physiological and pathological processes. This study aimed to investigate the regulatory role of CO released by CO-releasing molecule-2 (CORM-2) in a P2Y receptor-mediated calcium-signaling pathway in the human bronchial epithelial cell line, 16HBE14o-. METHODS: Intracellular calcium ([Ca2+]i) was measured by fura-2 microspectrofluorimetry. D-myo-inositol-1-phosphate (IP1) levels and cGMP-dependent protein kinase activity (PKG) were also quantified...
August 18, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28947610/regulating-protein-breakdown-through-proteasome-phosphorylation
#9
REVIEW
Jordan J S VerPlank, Alfred L Goldberg
The ubiquitin proteasome system degrades the great majority of proteins in mammalian cells. Countless studies have described how ubiquitination promotes the selective degradation of different cell proteins. However, there is a small but the growing literature that protein half-lives can also be regulated by post-translational modifications of the 26S proteasome. The present study reviews the ability of several kinases to alter proteasome function through subunit phosphorylation. For example, PKA (protein kinase A) and DYRK2 (dual-specificity tyrosine-regulated kinase 2) stimulate the proteasome's ability to degrade ubiquitinated proteins, peptides, and adenosine triphosphate, while one kinase, ASK1 (apoptosis signal-regulating kinase 1), inhibits proteasome function during apoptosis...
September 24, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28941685/gsk-3-mediates-no-cgmp-induced-isoflavone-production-in-soybean-sprouts
#10
Caifeng Jiao, Liangliang Zhu, Zhenxin Gu
The role of glycogen synthase kinase-3 (GSK-3) in the nitric oxide-guanosine 3',5'-cyclic monophosphate (NO-cGMP)-induced isoflavone production in soybean sprouts was examined. Inhibitors and donors of NO, cGMP, and GSK-3 inhibitor were added to UV-B irradiated sprouts. Results showed that NO, with cGMP, induced the expression of GSK-3 under UV-B radiation. Protein kinase G (PKG) was shown to be involved in NO-cGMP-induced GSK-3 activation. GSK-3 elevated activity and expression levels of chalcone synthase (CHS) and isoflavone synthase (IFS), and increased isoflavone accumulation...
November 2017: Food Research International
https://www.readbyqxmd.com/read/28935920/inhibition-of-pde2-reverses-beta-amyloid-induced-memory-impairment-through-regulation-of-pka-pkg-dependent-neuro-inflammatory-and-apoptotic-pathways
#11
Li Wang, Yilixiati Xiaokaiti, Gang Wang, Xiaoxiao Xu, Ling Chen, Xianfeng Huang, Li Liu, Jianchun Pan, Shuqun Hu, Zhuoyou Chen, Ying Xu
Beta amyloid peptides (Aβ) are known risk factors involved in cognitive impairment, neuroinflammatory and apoptotic processes in Alzheimer's disease (AD). Phosphodiesterase 2 (PDE2) inhibitors increase the intracellular cAMP and/or cGMP activities, which may ameliorate cognitive deficits associated with AD. However, it remains unclear whether PDE2 mediated neuroapoptotic and neuroinflammatory events, as well as cognitive performance in AD are related to cAMP/cGMP-dependent pathways. The present study investigated how the selective PDE2 inhibitor BAY60-7550 (BAY) affected Aβ-induced learning and memory impairment in two classic rodent models...
September 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28910498/phosphodiesterase-1a-inhibition-elicits-cgmp-dependent-relaxation-of-rat-mesenteric-arteries
#12
Makhala Michell Khammy, Thomas Dalsgaard, Peter Hjørringgaard Larsen, Claus Tornby Christoffersen, Dorte Clausen, Lars Kyhn Rasmussen, Lasse Folkersen, Morten Grunnet, Jan Kehler, Christian Aalkjaer, Jacob Nielsen
BACKGROUND AND PURPOSE: Phosphodiesterase 1 (PDE1), a subfamily of cyclic nucleotide phosphodiesterases consisting of three isoforms, PDE1A, PDE1B, and PDE1C, has been implicated in regulation of vascular tone. The PDE1 isoform(s) responsible for tone regulation is unknown. This study used isoform-preferring PDE1 inhibitors, Lu AF58027, Lu AF64196, Lu AF66896, and Lu AF67897, to investigate the relative contribution of PDE1 isoforms to regulation of vascular tone. EXPERIMENTAL APPROACH: In rat mesenteric arteries, expression and localisation of Pde1 isoforms were determined by qPCR and in situ hybridisation, and physiological impact of PDE1 inhibition were evaluated by isometric tension recordings...
September 14, 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28904134/an-ant-plant-mutualism-through-the-lens-of-cgmp-dependent-kinase-genes
#13
Pierre-Jean G Malé, Kyle M Turner, Manjima Doha, Ina Anreiter, Aaron M Allen, Marla B Sokolowski, Megan E Frederickson
In plant-animal mutualisms, how an animal forages often determines how much benefit its plant partner receives. In many animals, foraging behaviour changes in response to foraging gene expression or activation of the cGMP-dependent protein kinase (PKG) that foraging encodes. Here, we show that this highly conserved molecular mechanism affects the outcome of a plant-animal mutualism. We studied the two PKG genes of Allomerus octoarticulatus, an Amazonian ant that defends the ant-plant Cordia nodosa against herbivores...
September 13, 2017: Proceedings. Biological Sciences
https://www.readbyqxmd.com/read/28900930/cardiac-remodeling-and-disease-soce-and-trpc-signaling-in-cardiac-pathology
#14
Petra Eder
TRPC channels have been suggested as potential candidates mediating store-operated Ca(2+) entry (SOCE) in cardiomyocytes. There is increasing evidence that the TRPC isoforms TRPC1 and TRPC4 might fulfill the function as SOCs, in concert with or in parallel to the key players of SOCE, Orai1, and STIM1. Several other isoforms, e.g., TRPC3, TRPC6, and TRPC7, might rather associate to receptor-activated diacylglycerol (DAG)-sensitive ion channels. However, the exact activation mode has not been elucidated yet, given the characteristic of TRPC channels to heteromerize to unpredictable ion channel assemblies...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28880852/rna-sequencing-uncovers-molecular-mechanisms-underlying-pathological-complete-response-to-chemotherapy-in-patients-with-operable-breast-cancer
#15
Yongfeng Li, Xiaozhen Liu, Hongchao Tang, Hongjian Yang, Xuli Meng
BACKGROUND This study aimed to identify key genes contributing to pathological complete response (pCR) to chemotherapy by mRNA sequencing (RNA-seq). MATERIAL AND METHODS RNA was extracted from the frozen biopsy tissue of patients with pathological complete response and patients with non-pathological complete response. Sequencing was performed on the HiSeq2000 platform. Differentially expressed genes (DEGs) were identified between the pCR group and non-pCR (NpCR) group. Pathway enrichment analysis of DEGs was performed...
September 7, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28878687/no-sgc-pathway-modulates-ca-2-release-and-muscle-contraction-in-zebrafish-skeletal-muscle
#16
Zhou Xiyuan, Rainer H A Fink, Matias Mosqueira
Vertebrate skeletal muscle contraction and relaxation is a complex process that depends on Ca(2+) ions to promote the interaction of actin and myosin. This process can be modulated by nitric oxide (NO), a gas molecule synthesized endogenously by (nitric oxide synthase) NOS isoforms. At nanomolar concentrations NO activates soluble guanylate cyclase (sGC), which in turn activates protein kinase G via conversion of GTP into cyclic GMP. Alternatively, NO post-translationally modifies proteins via S-nitrosylation of the thiol group of cysteine...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28874661/a-potent-series-targeting-the-malarial-cgmp-dependent-protein-kinase-clears-infection-and-blocks-transmission
#17
David A Baker, Lindsay B Stewart, Jonathan M Large, Paul W Bowyer, Keith H Ansell, María B Jiménez-Díaz, Majida El Bakkouri, Kristian Birchall, Koen J Dechering, Nathalie S Bouloc, Peter J Coombs, David Whalley, Denise J Harding, Ela Smiljanic-Hurley, Mary C Wheldon, Eloise M Walker, Johannes T Dessens, María José Lafuente, Laura M Sanz, Francisco-Javier Gamo, Santiago B Ferrer, Raymond Hui, Teun Bousema, Iñigo Angulo-Barturén, Andy T Merritt, Simon L Croft, Winston E Gutteridge, Catherine A Kettleborough, Simon A Osborne
To combat drug resistance, new chemical entities are urgently required for use in next generation anti-malarial combinations. We report here the results of a medicinal chemistry programme focused on an imidazopyridine series targeting the Plasmodium falciparum cyclic GMP-dependent protein kinase (PfPKG). The most potent compound (ML10) has an IC50 of 160 pM in a PfPKG kinase assay and inhibits P. falciparum blood stage proliferation in vitro with an EC50 of 2.1 nM. Oral dosing renders blood stage parasitaemia undetectable in vivo using a P...
September 5, 2017: Nature Communications
https://www.readbyqxmd.com/read/28864549/atrial-natriuretic-peptide-anp-affects-stimulus-secretion-coupling-of-pancreatic-%C3%AE-cells
#18
Sabrina Undank, Julia Kaiser, Jelena Sikimic, Martina Düfer, Peter Krippeit-Drews, Gisela Drews
ANP influences glucose homeostasis and possibly acts as a link between the cardiovascular system and metabolism, especially in metabolic disorders like diabetes. The present study aimed to evaluate effects of ANP on β-cell function by the use of a β-cell specific knockout of the ANP receptor with guanylate cyclase activity (βGC-A-KO). ANP augmented insulin secretion at the threshold glucose concentration of 6 mM and decreased KATP single channel activity in β-cells of control mice but not of βGC-A-KO mice...
September 1, 2017: Diabetes
https://www.readbyqxmd.com/read/28855109/the-vasorelaxant-effect-of-mitiglinide-via-activation-of-voltage-dependent-k-channels-and-serca-pump-in-aortic-smooth-muscle
#19
Hongliang Li, Hye Won Kim, Sung Eun Shin, Mi Seon Seo, Jin Ryeol An, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Amy L Firth, Il-Whan Choi, Il Yong Han, Dae-Sung Lee, Mi-Jin Yim, Won Sun Park
AIMS: The vasorelaxant effects of the anti-diabetic drug, mitiglinide in phenylephrine (Phe)-pre-contracted aortic rings were examined. MATERIALS AND METHODS: Arterial tone measurement was performed in aortic smooth muscle cells. KEY FINDINGS: Mitiglinide dose-dependently induced vasorelaxation. Application of the large-conductance Ca(2+)-activated K(+) (BKCa) channel blocker paxilline, inwardly rectifying K(+) (Kir) channel blocker Ba(2+), and ATP-sensitive K(+) (KATP) channel blocker glibenclamide did not affect the vasorelaxant effect of mitiglinide...
November 1, 2017: Life Sciences
https://www.readbyqxmd.com/read/28808213/the-interaction-between-the-wnt-%C3%AE-catenin-signaling-cascade-and-pkg-activation-in-cancer
#20
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
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