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Cellular Signalling

Gabriel Carmona-Rosas, David A Hernández-Espinosa, Rocío Alcántara-Hernández, Marco A Alfonzo-Méndez, J Adolfo García-Sainz
The human α1D -adrenergic receptor is a seven transmembrane-domain protein that mediates many of the physiological actions of adrenaline and noradrenaline and participates in the development of hypertension and benign prostatic hyperplasia. We recently reported that different phosphorylation patterns control α1D -adrenergic receptor desensitization. However, to our knowledge, there is no data regarding the role(s) of this receptor's specific phosphorylation residues in its subcellular localization and signaling...
November 9, 2018: Cellular Signalling
Irmgard Tegeder
Nitric oxide is a versatile diffusible signaling molecule, whose biosynthesis by three NO synthases (NOS) is tightly regulated at transcriptional and posttranslational levels, availability of co-factors, and calcium binding. Above normal levels of NO have beneficial protective effects for example in the cardiovascular system, but also contribute to the pathophysiology in the context of inflammatory diseases, and to aging and neurodegeneration in the nervous system. The effect specificity relies on the functional and spatial specificity of the NOS isoenzymes, and on the duality of two major signaling mechanisms (i) activation of soluble guanylycylase (sGC)-dependent cGMP production and (ii) direct S-nitrosylation of redox sensitive cysteines of susceptible proteins...
November 5, 2018: Cellular Signalling
Songyot Anuchapreeda, Methee Rungrojsakul, Singkome Tima, Sawitree Chiampanichayakul, Sheryl R Krig
Earlier studies have revealed one function of the inhibitory mechanism of curcumin. Activating PKCα induces WT1 gene expression via signalling through downstream JNK and c-JUN. In the present study, the effect of c-JUN/AP-1 binding and transcriptional regulation of the WT1 gene promoter was investigated in K562 leukaemic cells. The non-cytotoxic dose (IC20 values) of curcumin (WT1 and AP-1 inhibitors) was employed to examine its effect on WT1 gene-mediated WT1 and AP-1 protein expression. Non-cytotoxic doses of both tanshinone IIA (AP-1 DNA-binding inhibitor) and SP600125 (JNK inhibitor) were used to test the role of c-JUN/AP-1 in WT1 gene expression...
November 3, 2018: Cellular Signalling
Koko Murakami, Joseph D Etlinger
Heterozygous germline mutations in the bone morphogenetic protein type II receptor gene (BMPRII) are associated with hereditary pulmonary arterial hypertension (HPAH). Missense mutations, both in the extracellular ligand-binding and cytoplasmic kinase domains, mostly involve substitution of conserved Cys residues. Singular substitution at any of those Cys residues causes cytoplasmic, perinuclear localization of BMPR with reduced cell surface expression and BMP signaling. The present study examined the effect of Cys residue substitution on BMPR endocytic trafficking and lysosome degradation...
November 2, 2018: Cellular Signalling
Johnna F Varghese, Rohit Patel, Umesh C S Yadav
Macrophage foam cell formation (FCF) has long been known to play a critical role during atherosclerotic plaque development. In the presence of atherogenic molecules such as oxidized low-density lipoprotein (oxLDL) macrophages accumulate massive amounts of lipid through uptake. However, in the presence of oxLDL mechanism of dysregulated lipid homeostasis in the macrophages remains largely unknown. Herein we have investigated the role of Sterol regulatory element binding protein (SREBP)-1 in oxLDL-induced inflammation and altered lipid homeostasis in macrophages...
October 31, 2018: Cellular Signalling
Shuang Yang, Dan Sun, Lining Wang, Xiuying Wang, Mai Shi, Xue Jiang, Xinran Gao
The kidney is one of the fastest-aging organs, and renal senescence has become a major disease affecting human health. Renal cellular senescence is regulated by the joint action of multiple signal transduction pathways. The previous study by our research group found that the Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway was involved in angiotensin II (Ang II)-induced senescence of human glomerular mesangial cells. However, the unique role of STAT3 activation in Ang II-induced senescence of human glomerular mesangial cells and the underlying mechanisms remain unclear...
October 30, 2018: Cellular Signalling
Man Zhang, Xin Jin, Yin-Feng Yang
The ruminal mucosal epithelium can secrete defensins, which play a key role in innate and adaptive immunity and are considered potential replacements for antibiotics. Of these, sheep β-defensin-1 (SBD-1) is one of the most potent molecules produced by ovine ruminal epithelial cells (ORECs). β-glucan, safe and effective immune activators, can stimulate innate and adaptive immune responses. Here we examined whether β-glucan from Saccharomyces cerevisiae can induce SBD-1 expression in ORECs, as well as the underlying mechanism...
October 26, 2018: Cellular Signalling
Takahiro Ishimoto, Yusuke Masuo, Yukio Kato, Noritaka Nakamichi
The promotion of neurogenesis is considered to be an effective therapeutic strategy for neuropsychiatric disorders because impairment of neurogenesis is associated with the onset and progression of these disorders. We have previously demonstrated that orally ingested ergothioneine (ERGO), a naturally occurring antioxidant and hydrophilic amino acid, promotes neurogenesis in the hippocampal dentate gyrus (DG) with its abundant neural stem cells (NSCs) and exerts antidepressant-like effects in mice. Independent of its antioxidant activities, ERGO induces in cultured NSCs this differentiation through induction of the basic helix-loop-helix transcription factor Math1...
October 22, 2018: Cellular Signalling
Zhencheng Li, Lui Näslund-Koch, Carlos Henriquez-Olguin, Jonas R Knudsen, Jingwen Li, Agnete B Madsen, Satoru Ato, Jacob Wienecke, Riki Ogasawara, Jens B Nielsen, Thomas E Jensen
Botulinum toxin A (botox) is a toxin used for spasticity treatment and cosmetic purposes. Botox blocks the excitation of skeletal muscle fibers by preventing the release of acetylcholine from motor nerves, a process termed chemical denervation. Surgical denervation is associated with increased expression of the canonical insulin-activated kinase Akt, lower expression of glucose handling proteins GLUT4 and hexokinase II (HKII) and insulin resistant glucose uptake, but it is not known if botox has a similar effect...
October 21, 2018: Cellular Signalling
Adriana Roura-Guiberna, Judith Hernandez-Aranda, Carlos Jorge Ramirez-Flores, Ricardo Mondragon-Flores, Nayely Garibay-Nieto, Gloria Queipo-Garcia, Estibalitz Laresgoiti-Servitje, Jae-Won Soh, Jesus Alberto Olivares-Reyes
Conjugated linoleic acid (CLA) constitutes a group of isomers derived from linoleic acid. Diverse studies have suggested that these unsaturated fatty acids have beneficial effects on human health. However, it has also been reported that their consumption can generate alterations in hepatic tissue. Thus, in the present study, we evaluated the effect of two of the major isomers of CLA, cis-9, trans-11-CLA and trans-10, cis-12-CLA, in the regulation of insulin signaling in a hepatic cell model, clone 9 (C9). We found that the two isomers decrease insulin-stimulated phosphorylation of the main proteins involved in insulin signaling, such as Akt at Ser473 and Thr308 , the insulin receptor at Tyr1158 , IRS-1 at Tyr632 , and GSK-3 at Ser9/21 ...
October 21, 2018: Cellular Signalling
Bradley S Ferguson, Heesun Nam, Ron F Morrison
Obesity is a strong predictor of heart disease, insulin resistance, and type II diabetes. Chronic, low-grade inflammation links obesity and insulin resistance through mitogen-activated protein kinase (MAPK) signaling pathways. Upstream kinases activate MAPK signaling, while MAPK-specific dual-specificity phosphatases (DUSPs) act as key modulators and controllers of MAPK deactivation (i.e. dephosphorylation). Using tumor necrosis factor α (TNFα) in 3 T3-L1 adipocytes as a model of inflammation, we report that TNFα-mediated induction of Dusp1, Dusp8 and Dusp16 modulated the transient regulation of MAPK (i...
October 19, 2018: Cellular Signalling
Pratap Karki, Angelo Meliton, Albert Sitikov, Yufeng Tian, Tomomi Ohmura, Anna A Birukova
Exposure to particulate matter (PM) associated with air pollution remains a major public health concern, as it has been linked to significant increase in cardiopulmonary morbidity and mortality. Lung endothelial cell (EC) dysfunction is one of the hallmarks of cardiovascular events of lung exposure to PM. However, the role of PM in acute lung injury (ALI) exacerbation and delayed recovery remains incompletely understood. This study tested a hypothesis that PM augments lung injury and EC barrier dysfunction via microtubule-dependent mechanisms...
October 16, 2018: Cellular Signalling
Long Bai, Hsun-Ming Chang, Yi-Min Zhu, Peter C K Leung
Lysyl oxidase (LOX) is a copper-dependent enzyme that maintains and stabilizes the extracellular matrix (ECM) by catalyzing the cross-linking of elastin and collagen. ECM within the ovarian follicle plays a crucial role in regulating follicular development and oocyte maturation. Bone morphogenetic protein 2 (BMP2) belongs to the BMP subfamily that has been shown to be involved in the process of ovarian folliculogenesis and luteal formation. To date, whether BMP2 regulates the activity of LOX during human follicular development remains to be elucidated...
October 12, 2018: Cellular Signalling
Daniel Markx, Julia Schuhholz, Michael Abadier, Sandra Beier, Mariana Lang, Barbara Moepps
In man, two CC chemokine receptor isoforms, CCR2a and CCR2b, are present that belong to the rhodopsin-like G protein-coupled receptor family, and couple to Gi and Gq family members. The CCR2 receptors are known to regulate canonical functions of chemokines such as directed migration of leukocytes, and to potentially control non-canonical functions such as differentiation, proliferation, and gene transcription of immune and non-immune cells. We recently reported on the activation of phospholipase C isoenzymes and RhoA GTPases by coupling of the two CCR2 receptors to members of the Gq family, in particular Gαq and Gα14 ...
October 12, 2018: Cellular Signalling
Xiao Zhang, Chen Miao, Zi Nan, Jialan Lyu, Yongmei Xi, Xiaohang Yang, Wanzhong Ge
Notch is a transmembrane receptor that mediates intercellular signaling through a conserved signaling cascade in all animal species. Transcriptional and posttranscriptional regulation of Notch receptor are important for maintaining Notch signaling activity. Here, we show that depletion of Drosophila Sin3A leads to loss of the adult wing margin and downregulation of Notch target gene expression in the developing wing disc. Sin3A regulates the Notch pathway downstream of Delta and upstream of Notch activation...
October 12, 2018: Cellular Signalling
Yue Li, Mengfei Yao, Tianqi Wu, Liyan Zhang, Yingying Wang, Liang Chen, Guohui Fu, Xiaoling Weng, Jianhua Wang
Lung cancer is a leading cause of cancer mortality worldwide with dramatically increasing incidence in recent years. However, the mechanism underlying its progression remains unclear. The aim of this study was to identify the role of hypermethylated in cancer 1 (HIC1) in lung cancer development. Here we found that HIC1 expression was markedly decreased in lung cancer compared with the corresponding adjacent non-cancerous tissues. Meanwhile, overall survival (OS) of lung cancer patients was negatively related with HIC1 expression using TCGA and GEO datasets...
October 10, 2018: Cellular Signalling
Zsuzsa Jenei-Lanzl, Andrea Meurer, Frank Zaucke
Osteoarthritis (OA) can be regarded as a chronic, painful and degenerative disease that affects all tissues of a joint and one of the major endpoints being loss of articular cartilage. In most cases, OA is associated with a variable degree of synovial inflammation. A variety of different cell types including chondrocytes, synovial fibroblasts, adipocytes, osteoblasts and osteoclasts as well as stem and immune cells are involved in catabolic and inflammatory processes but also in attempts to counteract the cartilage loss...
October 9, 2018: Cellular Signalling
So-Yeon Nam, Soo-Jin Park, Dong-Soon Im
Although GPR35 is an orphan G protein-coupled receptor, synthetic agonists and antagonists have been developed. Recently, cromolyn, a mast cell stabilizer, was reported as an agonist of GPR35 and was shown to exhibit antifibrotic effects through its actions on hepatocytes and stellate cells. In this study, the role of GPR35 in hepatic steatosis was investigated using an in vitro model of liver X receptor (LXR)-mediated hepatocellular steatosis and an in vivo model of high fat diet-induced liver steatosis. GPR35 was expressed in Hep3B human hepatoma cells and mouse primary hepatocytes...
October 7, 2018: Cellular Signalling
Josiah E Hardesty, Banrida Wahlang, K Cameron Falkner, Hongxue Shi, Jian Jin, Daniel Wilkey, Michael Merchant, Corey Watson, Russell A Prough, Matthew C Cave
BACKGROUND: Polychlorinated biphenyl-mediated steatohepatitis has been shown to be due in part to inhibition of epidermal growth factor receptor (EGFR) signalling. EGFR signalling regulates many facets of hepatocyte function, but it is unclear which other kinases and pathways are involved in the development of toxicant-associated steatohepatitis (TASH). METHODS: Comparative hepatic phosphoproteomic analysis was used to identify which kinases were affected by either PCB exposure (Aroclor 1260 mixture), high fat diet (HFD), or their interaction in a chronic exposure model of TASH...
October 6, 2018: Cellular Signalling
Murali K Yanda, Qiangni Liu, Valeriu Cebotaru, William B Guggino, Liudmila Cebotaru
Autosomal dominant polycystic kidney disease (ADPKD) is caused by mutations in genes encoding the polycystin (PC) 1 and 2 proteins. The goal of this study was to determine the role of calcium in regulating cyst growth. Stromal interaction molecule 1 (STIM1) protein expression was 15-fold higher in PC1-null proximal tubule cells (PN) than in heterozygote (PH) controls and 2-fold higher in an inducible, PC1 knockout, mouse model of ADPKD compared to a non-cystic match control. IP3 receptor protein expression was also higher in the cystic mice...
October 5, 2018: Cellular Signalling
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