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https://www.readbyqxmd.com/read/29351415/amp-activated-protein-kinase-and-adenosine-are-both-metabolic-modulators-regulating-chloride-secretion-in-the-shark-rectal-gland-squalus-acanthias
#1
Rugina I Neuman, Juliette A M van Kalmthout, Daniel J Pfau, Dhariyat M Menendez, Lawrence H Young, John N Forrest
The production of endogenous adenosine during secretagogue stimulation of CFTR leads to feedback inhibition limiting further chloride secretion in the rectal gland of the dogfish shark (Squalus acanthias). In the present study, we examined the role of AMP-kinase (AMPK) as an energy sensor also modulating chloride secretion through CFTR. We found that glands perfused with forskolin and isobutylmethylxanthine (F + I), potent stimulators of chloride secretion in this ancient model, caused significant phosphorylation of the catalytic subunit Thr172 of AMPK...
December 20, 2017: American Journal of Physiology. Cell Physiology
https://www.readbyqxmd.com/read/29348469/treprostinil-inhibits-proliferation-and-extracellular-matrix-deposition-by-fibroblasts-through-camp-activation
#2
Christopher Lambers, Michael Roth, Peter Jaksch, Gabriella Muraközy, Michael Tamm, Walter Klepetko, Bahil Ghanim, Feng Zhao
Idiopathic pulmonary fibrosis (IPF) is characterized by peripheral lung fibrosis and increased interstitial extracellular matrix (ECM) deposition. In IPF, tumor growth factor (TGF)-β1 which is the major stimulus of ECM deposition, and platelet derived growth factor (PDGF)-BB is a potent stimulus of fibrosis. Thus, the effect of Treprostinil on TGF-ß1 and PDGF-induced fibroblast proliferation and ECM deposition was investigated. Human peripheral lung fibroblasts of seven IPF patients and five lung donors were stimulated by PDGF, or TGF-β1, or the combination...
January 18, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29346269/identification-of-secreted-proteins-involved-in-nonspecific-dsrna-mediated-lutzomyia-longipalpis-ll5-cell-antiviral-response
#3
Andrea Martins-da-Silva, Erich Loza Telleria, Michel Batista, Fabricio Klerynton Marchini, Yara Maria Traub-Csekö, Antonio Jorge Tempone
Hematophagous insects transmit infectious diseases. Sand flies are vectors of leishmaniasis, but can also transmit viruses. We have been studying immune responses of Lutzomyia longipalpis, the main vector of visceral leishmaniasis in the Americas. We identified a non-specific antiviral response in L. longipalpis LL5 embryonic cells when treated with non-specific double-stranded RNAs (dsRNAs). This response is reminiscent of interferon response in mammals. We are investigating putative effectors for this antiviral response...
January 18, 2018: Viruses
https://www.readbyqxmd.com/read/29344249/estradiol-suppresses-phosphorylation-of-er%C3%AE-serine-167-through-upregulation-of-pp2a-in-breast-cancer-cells
#4
Takanori Hayashi, Masahiro Hikichi, Jun Yukitake, Nobuhiro Harada, Toshiaki Utsumi
Aromatase inhibitors (AIs) are effective endocrine therapeutics for postmenopausal women with estrogen receptor (ER)α-positive breast cancer. However, the efficacy of the treatment is often limited by the onset of AI resistance, owing to the phosphorylation of ERα serine 167 (Ser167). Previous studies have indicated that hyperactivation of the phosphoinositide-3 kinase/RAC serine/threonine-protein kinase signaling pathway occurs in AI-resistant breast cancer models, which coincides with elevated levels of ERα phosphorylation at Ser167...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29342125/induction-of-pro-apoptotic-endoplasmic-reticulum-stress-in-multiple-myeloma-cells-by-neo214-perillyl-alcohol-conjugated-to-rolipram
#5
Thomas C Chen, Nymph Chan, Shirin Labib, Jiali Yu, Hee-Yeon Cho, Florence M Hofman, Axel H Schönthal
Despite the introduction of new therapies for multiple myeloma (MM), many patients are still dying from this disease and novel treatments are urgently needed. We have designed a novel hybrid molecule, called NEO214, that was generated by covalent conjugation of the natural monoterpene perillyl alcohol (POH), an inducer of endoplasmic reticulum (ER) stress, to rolipram (Rp), an inhibitor of phosphodiesterase-4 (PDE4). Its potential anticancer effects were investigated in a panel of MM cell lines. We found that NEO214 effectively killed MM cells in vitro with a potency that was over an order of magnitude stronger than that of its individual components, either alone or in combination...
January 17, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29329032/targeting-expression-of-adenosine-receptors-during-hypoxia-induced-angiogenesis-a-study-using-zebrafish-model
#6
Navina Panneerselvan, Malathi Ragunathan
Hypoxia is known to be a major player during pathological angiogenesis and adenosine as a negative feedback signaling to maintain oxygen delivery in pathological ischemic condition. We mimicked hypoxic condition and studied angiogenesis by inducing adenosine receptors using forskolin, a plant compound and NECA analogue of adenosine using zebrafish model. Vascular endothelial growth factor (VEGF) is known to play a key role during pathological angiogenesis and regulated by the factors HIF1a under hypoxic condition and recently Notch is proposed to play a negative feedback loop mechanism along with VEGF signaling but the role of adenosine receptor during the process is not known...
January 9, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29328471/prostaglandin-e2-receptor-ep4-is-involved-in-the-cell-growth-and-invasion-of-prostate-cancer-via-the-camp%C3%A2-pka-pi3k%C3%A2-akt-signaling-pathway
#7
Song Xu, Wenquan Zhou, Jingping Ge, Zhengyu Zhang
Prostate cancer (PCa) is one of the most prevalent diagnosed malignancies globally. Previous studies have demonstrated that prostaglandin E2 (PGE2) is closely associated with the tumorigenesis and progression of PCa. However, the underlying molecular mechanisms remain unclear and require further investigation. Matrix metalloproteinases (MMPs), receptor activator of nuclear factor‑κB ligand (RANKL) and runt‑related transcription factor 2 (RUNX2), which are involved in cell growth and bone metastasis, are frequently activated or overexpressed in various types of cancer, including PCa...
January 9, 2018: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29328434/chemical-conversion-of-human-lung-fibroblasts-into-neuronal-cells
#8
Xiao-Yu Wan, Li-Yun Xu, Bing Li, Qiu-Hong Sun, Qiu-Liang Ji, Dong-Dong Huang, Lan Zhao, Yong-Tao Xiao
It has been previously reported that human embryonic fibroblasts and mouse embryonic fibroblasts can be converted into neuronal cells using chemical agents, along with forced expression specific transcriptional factors. However, the materials required for reprogramming in these approaches presents major technical difficulties and safety concerns. The current study investigated whether a cocktail of small molecules can convert human lung fibroblast cells into neurons. The small molecules valproic acid, CHIR99021, DMH1, Repsox, forskolin, Y‑27632 and SP600125 (VCHRFYS) were used to induce MRC‑5 cells into neuronal cells in vitro...
January 10, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29327289/study-of-adenylyl-cyclase-g%C3%AE-s-interactions-and-identification-of-novel-ac-ligands
#9
Appalaraju Jaggupilli, Premnath Dhanaraj, Alexander Pritchard, John L Sorensen, Shyamala Dakshinamurti, Prashen Chelikani
Adenylyl cyclases (ACs) are membrane bound enzymes that catalyze the production of cAMP from ATP in response to the activation by G-protein Gαs. Different isoforms of ACs are ubiquitously expressed in different tissues involved in regulatory mechanisms in response to specific stimulants. There are 9 AC isoforms present in humans, with AC5 and AC6 proposed to play a vital role in cardiac functions. The activity of AC6 is sensitive to nitric oxide, such that nitrosylation of the protein might regulate its function...
January 11, 2018: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/29310813/effect-of-sevoflurane-on-the-atpase-activity-of-hippocampal-neurons-in-a-rat-model-of-cerebral-ischemia-reperfusion-injury-via-the-camp-pka-signaling-pathway
#10
Tie-Jun Liu, Jin-Cun Zhang, Xiao-Zeng Gao, Zhi-Bin Tan, Jian-Jun Wang, Pan-Pan Zhang, Ai-Bin Cheng, Shu-Bo Zhang
We aim to investigate the effects of sevoflurane on the ATPase activity of the hippocampal neurons in rats with cerebral ischemia-reperfusion injury (IRI) via the cyclic adenosine monophosphate (cAMP) and protein kinase A (PKA) signaling pathway. Sixty rats were assigned into the normal, model and sevoflurane groups (n = 20, the latter two groups were established as focal cerebral IRI models). The ATPase activity was detected using an ultramicro Na (+)-K (+)-ATP enzyme kit. Immunohistochemical staining was used to detect the positive protein expression of cAMP and PKA...
January 2018: Kaohsiung Journal of Medical Sciences
https://www.readbyqxmd.com/read/29305607/novel-insight-into-the-role-of-cftr-in-lacrimal-gland-duct-function-in-mice
#11
Orsolya Berczeli, Eszter Vizvári, Máté Katona, Dénes Török, László Szalay, Ferenc Rárosi, István Németh, Zoltán Rakonczay, Péter Hegyi, Chuanqing Ding, Edit Tóth-Molnár
Purpose: The role of cystic fibrosis transmembrane conductance regulator (CFTR) in lacrimal gland (LG) function has only recently received some attention, mainly from our group. In the present study, we investigated the potential changes of LG pathology, tear secretion, ocular surface integrity, and fluid secretion in isolated LG ducts from CFTR knockout (KO) mice. Methods: Tear production and ocular surface integrity were investigated in anesthetized wild-type (WT) and KO mice using cotton threads and fluorescein staining, respectively...
January 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29301980/mir-210-and-gpd1l-regulate-edn2-in-primary-and-immortalized-human-granulosa-lutein-cells
#12
Ketan Shrestha, Adepeju Esther Onasanya, Iris Eisenberg, Noa Wigoda, Simcha Yagel, Ronit Yalu, Rina Meidan, Tal Imbar
Endothelin-2 (EDN2), expressed at a narrow window during the periovulatory period, critically affects ovulation and corpus luteum (CL) formation. LH (acting mainly via cAMP) and hypoxia are implicated in CL formation; therefore, we aimed to elucidate how these signals regulate EDN2 using human primary (hGLCs) and immortalized (SVOG) granulosa-lutein cells. The hypoxiamiR, microRNA-210 (miR-210) was identified as a new essential player in EDN2 expression. Hypoxia (either mimetic compound-CoCl2, or low O2) elevated hypoxia inducible factor 1A (HIF1A), miR-210, and EDN2...
January 4, 2018: Reproduction: the Official Journal of the Society for the Study of Fertility
https://www.readbyqxmd.com/read/29283200/forskolin-ameliorates-mancozeb-induced-testicular-and-epididymal-toxicity-in-wistar-rats-by-reducing-oxidative-toxicity-and-by-stimulating-steroidogenesis
#13
B P Girish, P Sreenivasula Reddy
In the present study, we have tested the beneficial effects of forskolin in protecting the mancozeb-induced reproductive toxicity in rats. Adult male Wistar rats were exposed to either mancozeb (500 mg/kg body weight/day) or forskolin (5 mg/kg body weight/day) or both for 65 days and analyzed for spermatogenesis and steroidogenesis and testicular and epididymal oxidative toxicity. A significant decrease in daily sperm production, epididymal sperm count, motile, viable, and hypo-osmotic swelling-tail swelled sperm was observed in mancozeb-treated rats...
December 28, 2017: Journal of Biochemical and Molecular Toxicology
https://www.readbyqxmd.com/read/29282201/mondoa-is-an-essential-glucose-responsive-transcription-factor-in-human-pancreatic-beta-cells
#14
Paul Richards, Latif Rachdi, Masaya Oshima, Piero Marchetti, Marco Bugliani, Mathieu Armanet, Catherine Postic, Sandra Guilmeau, Raphael Scharfmann
While the mechanisms by which glucose regulates insulin secretion from pancreatic beta cells are now well described, the way glucose modulates gene expression in such cells needs more understanding. Here, we demonstrate that MondoA, but not its paralogue ChREBP, is the predominant glucose-responsive transcription factor in human pancreatic beta EndoC-βH1 cells and in human islets. In high glucose conditions, MondoA shuttles to the nucleus where it is required for the induction of the glucose-responsive genes ARRDC4 and TXNIP, the latter being a protein strongly linked to beta-cell dysfunction and diabetes...
December 27, 2017: Diabetes
https://www.readbyqxmd.com/read/29281259/development-of-arrayed-colonic-organoids-for-screening-of-secretagogues-associated-with-enterotoxins
#15
Dulan B Gunasekara, Matthew Disalvo, Yuli Wang, Daniel Nguyen, Mark I Reed, Jennifer Speer, Christopher E Sims, Scott T Magness, Nancy L Allbritton
Enterotoxins increase intestinal fluid secretion through the modulation of ion channels as well as activating the enteric nervous and immune systems. Colonic organoids, also known as colonoids, are functionally and phenotypically similar to in vivo colonic epithelium, and have been used to study intestinal ion transport and subsequent water flux in physiology and disease models. In conventional cultures, organoids exist as spheroids embedded within a hydrogel patty of extracellular matrix, and form at multiple depths impairing efficient imaging which is necessary to capture data from statistically relevant sample sizes...
December 27, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/29277372/effects-of-chlorogenic-acid-on-carbachol-induced-contraction-of-mouse-urinary-bladder
#16
Takeharu Kaneda, Noriyasu Sasaki, Norimoto Urakawa, Kazumasa Shimizu
Chlorogenic acid (CGA) is a polyphenol found in coffee and medicinal herbs such as Lonicera japonica. In this study, the effect of CGA-induced relaxation on carbachol (CCh)-induced contraction of mouse urinary bladder was investigated. CGA (30-300 μg/ml) inhibited CCh- or U46619-induced contraction in a concentration-dependent manner. SQ22536 (adenylyl cyclase inhibitor) recovered CGA-induced relaxation of CCh-induced contraction; however, ODQ (guanylyl cyclase inhibitor) did not have the same effect. In addition, 3-isobutyl-1-methylxanthine (IBMX) enhanced CGA-induced relaxation; however, forskolin or sodium nitroprusside did not have the same effect...
December 15, 2017: Journal of Pharmacological Sciences
https://www.readbyqxmd.com/read/29276973/molecular-and-functional-characterization-of-tumor-induced-factor-tif-hamster-homolog-of-cxcl3-gro%C3%AE-displays-tumor-suppressive-activity
#17
Lili Jin, Zhou-Fang Li, Da-Kui Wang, Meina Sun, Wei Qi, Qiang Ma, Li Zhang, Chun Chu, Elaine Y M Chan, Susanna S T Lee, Helen Wise, Ka-Fai To, Ying Shi, Naiming Zhou, Wing-Tai Cheung
Previously our lab has created a mouse ovarian xenograft model of copy number variation (CNV)-mediated G protein-coupled receptor (GPCR) MAS-driven tumorigenesis, and RNA profiling identified a putative chemokine tumor-induced factor (Tif). Sequence analysis and chemotactic study suggested that Tif was likely to be a hamster homolog of human GROγ (CXCL3) [IJC 125 (2009): 1316-1327]. In the present study, we report the molecular and functional characterization of the Tif gene. Genomic study of CHO-K1 cells indicated that Tif gene consisted of 4 exons, characterized with an antisense B1 element which is embedded in the fourth exon...
December 22, 2017: Cytokine
https://www.readbyqxmd.com/read/29262264/pde8-is-expressed-in-human-airway-smooth-muscle-and-selectively-regulates-camp-signaling-by-%C3%AE-2ar-ac6
#18
Timothy B Johnstone, Kaitlyn H Smith, Cynthia J Koziol-White, Fengying Li, Austin G Kazarian, Maia L Corpuz, Maya Shumyatcher, Frederick J Ehlert, Blanca E Himes, Reynold A Panettieri, Rennolds S Ostrom
Two cAMP signaling compartments centering around adenylyl cyclase (AC) exist in human airway smooth muscle (HASM) cells, one containing ß2AR-AC6 and another containing E prostanoid receptors (EPR)-AC2. We hypothesized that different phosphodiesterase (PDE) isozymes selectively regulate cAMP signaling in each compartment. According to RNA-seq data, 18 of 24 PDE genes were expressed in primary HASM cells derived from age- and gender-matched donors with and without asthma. PDE8A was the third most abundant of the cAMP-degrading PDE genes, after PDE4A and PDE1A...
December 20, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/29249695/gdc-0879-a-brafv600e-inhibitor-protects-kidney-podocytes-from-death
#19
Jonas Sieber, Nicolas Wieder, Abbe Clark, Manuel Reitberger, Sofia Matan, Jeannine Schoenfelder, Jianming Zhang, Anna Mandinova, Joshua Adam Bittker, Juan Gutierrez, Ozan Aygün, Namrata Udeshi, Steven Carr, Peter Mundel, Andreas Werner Jehle, Anna Greka
Progressive kidney diseases affect approximately 500 million people worldwide. Podocytes are terminally differentiated cells of the kidney filter, the loss of which leads to disease progression and kidney failure. To date, there are no therapies to promote podocyte survival. Drug repurposing may therefore help accelerate the development of cures in an area of tremendous unmet need. In a newly developed high-throughput screening assay of podocyte viability, we identified the BRAFV600E inhibitor GDC-0879 and the adenylate cyclase agonist forskolin as podocyte-survival-promoting compounds...
December 6, 2017: Cell Chemical Biology
https://www.readbyqxmd.com/read/29247588/oocyte-maturation-in-the-toad-rhinella-arenarum-amphibia-anura-evidence-of-camp-involvement-in-steroid-production-and-action
#20
Ana Josefina AriasTorres, José Bernardino Páez, Liliana Isabel Zelarayán
In this work, we describe the participation of the Adenylate cyclase/3'-5'-cyclic adenonsine monophosphate (cAMP) pathway in the seasonal follicular secretion of progesterone (P4 ) and testosterone (T), and its relationship with the maturation of Rhinella arenarum oocytes. Under gonadotropin stimulation, P4 secretion was the dominant steroid produced during the reproductive period, resulting in 100% germinal vesicle breakdown (GVBD) in oocytes in vitro; in contrast, T and estradiol (E2 ) secretion increased (∼16 nM/20 follicles and ∼80 pM/20 follicles, respectively) during the non-reproductive period, but only yielded 50% GVBD...
December 16, 2017: Molecular Reproduction and Development
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