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https://www.readbyqxmd.com/read/28328746/cross-talk-between-insulin-signaling-and-gpcrs
#1
Qin Fu, Qian Shi, Toni M West, Yang K Xiang
Diabetes is a major risk factor for the development of heart failure. One of the hallmarks of diabetes is insulin resistance associated with hyperinsulinemia. The literature shows that insulin and adrenergic signaling is intimately linked to each other; however, whether and how insulin may modulate cardiac adrenergic signaling and cardiac function remains unknown. Notably, recent studies have revealed that insulin receptor and β2 adrenergic receptor (β2AR) forms a membrane complex in animal hearts, bringing together the direct contact between two receptor signaling systems, and forming an integrated and dynamic network...
March 17, 2017: Journal of Cardiovascular Pharmacology
https://www.readbyqxmd.com/read/28327750/dynamic-studies-of-the-interaction-of-a-ph-responsive-amphiphilic-polymer-with-a-dopc-lipid-membrane
#2
Sivaramakrishnan Ramadurai, Marco Werner, Nigel K H Slater, Aaron Martin, Vladimir A Baulin, Tia E Keyes
Deeper understanding of the molecular interactions between polymeric materials and the lipid membrane is important across a range of applications from permeation for drug delivery to encapsulation for immuno-evasion. Using highly fluidic microcavity supported lipid bilayers, we studied the interactions between amphiphilic polymer PP50 and a DOPC lipid bilayer. As the PP50 polymer is pH responsive the studies were carried out at pH 6.5, 7.05 and 7.5, corresponding to fully, partly protonated (pH = pKa = 7.05) and fully ionized states of the polymer, respectively...
March 22, 2017: Soft Matter
https://www.readbyqxmd.com/read/28327597/molecular-signaling-underlying-bulleyaconitine-a-baa-induced-microglial-expression-of-prodynorphin
#3
Teng-Fei Li, Hai-Yun Wu, Yi-Rui Wang, Xin-Yan Li, Yong-Xiang Wang
Bulleyaconitine (BAA) has been shown to possess antinociceptive activities by stimulation of dynorphin A release from spinal microglia. This study investigated its underlying signal transduction mechanisms. The data showed that (1) BAA treatment induced phosphorylation of CREB (rather than NF-κB) and prodynorphin expression in cultured primary microglia, and antiallodynia in neuropathy, which were totally inhibited by the CREB inhibitor KG-501; (2) BAA upregulated phosphorylation of p38 (but not ERK or JNK), and the p38 inhibitor SB203580 (but not ERK or JNK inhibitor) and p38β gene silencer siRNA/p38β (but not siRNA/p38α) completely blocked BAA-induced p38 phosphorylation and/or prodynorphin expression, and antiallodynia; (3) BAA stimulated cAMP production and PKA phosphorylation, and the adenylate cyclase inhibitor DDA and PKA inhibitor H-89 entirely antagonized BAA-induced prodynorphin expression and antiallodynia; (4) The Gs-protein inhibitor NF449 completely inhibited BAA-increased cAMP level, prodynorphin expression and antiallodynia, whereas the antagonists of noradrenergic, corticotrophin-releasing factor, A1 adenosine, formyl peptide, D1/D2 dopamine, and glucagon like-peptide-1 receptors failed to block BAA-induced antiallodynia...
March 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28326667/the-v2-receptor-antagonist-tolvaptan-raises-cytosolic-calcium-and-prevents-aqp2-trafficking-and-function-an-in-vitro-and-in-vivo-assessment
#4
Grazia Tamma, Annarita Di Mise, Marianna Ranieri, Ari Geller, Roberto Tamma, Alberta Zallone, Giovanna Valenti
Tolvaptan, a selective vasopressin V2 receptor antagonist, is a new generation diuretic. Its clinical efficacy is in principle due to impaired vasopressin-regulated water reabsorption via aquaporin-2 (AQP2). Nevertheless, no direct in vitro evidence that tolvaptan prevents AQP2-mediated water transport, nor that this pathway is targeted in vivo in patients with syndrome of inappropriate antidiuresis (SIAD) has been provided. The effects of tolvaptan on the vasopressin-cAMP/PKA signalling cascade were investigated in MDCK cells expressing endogenous V2R and in mouse kidney...
March 21, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28324237/cyclosporine-a-induces-endoplasmic-reticulum-stress-and-influences-pro-apoptotic-factors-in-human-gingival-fibroblasts
#5
Suresh Ranga Rao, Shiyamali Sundararajan, Rajasekaran Subbarayan, Dinesh Murugan Girija
Cyclosporine-A (CsA) induces gingival overgrowth. Cyclosporine's anti-apoptotic activity in human gingival fibroblast is due to desensitization of mitochondrial permeability transition pore (MPTP) and augmentation of anti-apoptotic, Bcl2. Alternative mechanisms of apoptosis exist involving enzymes like calcium-dependent Calpain and signaling events related to apoptosis, like Glycogen synthase kinase 3β (GSK3β) and protein kinase A (PKA). Cyclosporine-A in renal tubular cells induces endoplasmic reticulum stress (ER stress) which has not been explored in gingival overgrowth...
March 21, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28324013/acute-parathyroid-hormone-injection-increases-c-terminal-but-not-intact-fibroblast-growth-factor-23-levels
#6
V M Knab, B Corbin, O Andrukhova, J M Hum, P Ni, S Rabadi, A Maeda, K E White, R G Erben, H Jüppner, M Christov
The acute effects of PTH on FGF23 in vivo are not well understood. After a single s.c. PTH(1-34) injection (50nmol/kg) in mice, FGF23 levels were assessed in plasma using assays that measure either intact alone (iFGF23) or intact/C-terminal FGF23 (cFGF23). Furthermore, FGF23 mRNA and protein levels were assessed in bone. In addition, we examined the effects of PTH treatment on FGF23 production in vitro using differentiated calvarial osteocyte-like cells. cFGF23 levels increased by 3-5-fold within two hours following PTH injection, which returned to baseline by 4 hours...
January 23, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323939/tac1-gene-products-regulate-pituitary-hormone-secretion-and-gene-expression-in-prepubertal-grass-carp-pituitary-cells
#7
Guangfu Hu, Mulan He, Wendy K W Ko, Anderson O L Wong
Tachykinin 1 (TAC1) is known to have diverse functions in mammals but similar information is scarce in lower vertebrates including fish species. Using grass carp as a model, the pituitary actions, receptor specificity and post-receptor signaling of TAC1 gene products, namely substance P (SP) and neurokinin A (NKA), were examined. As a first step, TAC1 encoding carp SP and NKA as well as tachykinin receptors NK1R and NK2R were cloned in carp pituitary. Expression studies revealed that the newly cloned receptors were functional and with pharmacological properties similar to mammalian counterparts...
March 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323246/the-role-of-spinal-gabab-receptors-in-cancelr-induced-bone-pain-in-rats
#8
Ya-Qun Zhou, Shu-Ping Chen, Dai-Qiang Liu, Anne Manyande, Wen Zhang, Shao-Bing Yang, Bing-Rui Xiong, Qiao-Chu Fu, Zhen-Peng Song, Heike Rittner, Da-Wei Ye, Yu-Ke Tian
Cancer-induced bone pain (CIBP) remains a major challenge in advanced cancer patients due to our lack of understanding of its mechanisms. Previous studies have demonstrated the vital role of GABAB receptors (GABABRs) in regulating nociception and various neuropathic pain models have shown diminished activity of GABABRs. However, the role of spinal GABABRs in CIBP remains largely unknown. In this study, we investigated the specific cellular mechanisms of GABABRs in the development and maintenance of CIBP in rats...
March 18, 2017: Journal of Pain: Official Journal of the American Pain Society
https://www.readbyqxmd.com/read/28322461/iodinated-tg-in-thyroid-follicular-lumen-regulates-ttf-1-and-pax8-expression-via-tsh-tshr-signaling-pathway
#9
Huibin Huang, Yaxiong Shi, Bo Liang, Huiyao Cai, Qingyan Cai
Our previous study showed that highly iodinated thyroglobulin (TG) inhibited thyroid transcription factor-1 (TTF-1) and paired box gene 8 (PAX8) expression, but the potential mechanism remains unclear. In this study, we constructed a thyroid follicle model in vitro to mimic its natural physiological structure and explored how iodinated TG in the follicular lumen tuned TTF-1 and PAX8 expression. Our data showed that lowly iodinated TG enhanced PKA activity while upregulation of both TTF-1 and PAX8 expression; and that highly iodinated TG triggered PKC activity while suppression of TTF-1 and PAX8 expression...
March 21, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28322447/regulation-role-of-crtc3-in-skeletal-muscle-and-adipose-tissue
#10
REVIEW
Jiaqi Liu, Ziye Xu, Weiche Wu, Yizhen Wang, Tizhong Shan
The cyclic adenosine monophosphate (cAMP) - protein kinase A (PKA) signaling pathway plays important role in regulating energy homeostasis. Many of the effects of the cAMP-PKA signaling is mediated through the cAMP responsive element binding protein (CREB) and its coactivator CREB-regulated transcription coactivators (CRTCs). CRTC3 is a member of CRTCs family proteins and plays important roles in glucose and energy metabolism. Previous studies shown that global knockout of CRTC3 enhances oxygen consumption and energy expenditure and subsequently protects the knockout animal against obesity...
March 21, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28321180/multiple-kinases-involved-in-the-nicotinic-modulation-of-gamma-oscillations-in-the-rat-hippocampal-ca3-area
#11
JianGang Wang, XiaoLong He, Fangli Guo, XiangLin Cheng, Yali Wang, XiaoFang Wang, ZhiWei Feng, Martin Vreugdenhil, ChengBiao Lu
Neuronal synchronization at gamma band frequency (20-80 Hz, γ oscillations) is closely associated with higher brain function, such as learning, memory and attention. Nicotinic acetylcholine receptors (nAChRs) are highly expressed in the hippocampus, and modulate hippocampal γ oscillations, but the intracellular mechanism underlying such modulation remains elusive. We explored multiple kinases by which nicotine can modulate γ oscillations induced by kainate in rat hippocampal area CA3 in vitro. We found that inhibitors of cyclic AMP dependent kinase (protein kinase A, PKA), protein kinase C (PKC), N-methyl-D-aspartate receptor (NMDA) receptors, Phosphoinositide 3-kinase (PI3K) and extracellular signal-related kinases (ERK), each individually could prevent the γ oscillation-enhancing effect of 1 μM nicotine, whereas none of them affected baseline γ oscillation strength...
2017: Frontiers in Cellular Neuroscience
https://www.readbyqxmd.com/read/28319060/the-anti-diabetic-drug-exenatide-a-glucagon-like-peptide-1-receptor-agonist-counteracts-hepatocarcinogenesis-through-camp-pka-egfr-stat3-axis
#12
M Zhou, M T S Mok, H Sun, A W Chan, Y Huang, A S L Cheng, G Xu
Epidemiological studies have demonstrated a close association of type 2 diabetes and hepatocellular carcinoma (HCC). Exenatide (Ex-4), a potent diabetes drug targeting glucagon-like peptide-1 receptor (GLP-1R), is protective against non-alcoholic fatty liver disease (NAFLD). However, the Ex-4 function and GLP-1R status have yet been explored in HCC. Herein we investigated the effect of Ex-4 in diethylnitrosamine (DEN)-treated mice consuming control or high-fat high-carbohydrate diet. Administration of Ex-4 significantly improved obesity-induced hyperglycemia and hyperlipidemia and reduced HCC multiplicity in obese DEN-treated mice, in which suppressed proliferation and induced apoptosis were confined to tumor cells...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318907/the-effects-of-mutating-tyr9-and-arg15-on-the-structure-stability-conformational-dynamics-and-mechanism-of-gsta3-3
#13
Gary J Robertson, Stoyan H Stoychev, Yasien Sayed, Ikechukwu Achilonu, Heini W Dirr
Glutathione S-transferase A3-3 is the most catalytically efficient steroid isomerase enzyme known in humans, transforming Δ(5)-androstene-3-17-dione into Δ(4)-androstene-3-17-dione. GSTA3-3 catalyzes this reaction with ten-fold greater efficiency than GSTA1-1, its closest competitor in the Alpha class of GSTs. In order to examine the differences between Alpha class GSTs and to better elucidate the mechanism of GSTA3-3 the roles of Tyr9 and Arg15 were examined. Tyr9 is the major catalytic residue of Alpha class GSTs and Arg15 is proposed to be catalytically important to GSTA3-3 but never before experimentally examined...
March 1, 2017: Biophysical Chemistry
https://www.readbyqxmd.com/read/28315374/glp-1-analogue-cjc-1131-prevents-amyloid-%C3%AE-protein-induced-impirments-of-spatial-memory-and-synaptic-plasticity-in-rats
#14
Sheng-Xiao Zhang, Hong-Yan Cai, Xiao-Wen Ma, Li Yuan, Jun Zhang, Zhao-Jun Wang, Yu-Feng Li, Jin-Shun Qi
Although amyloid β protein (Aβ) has been recognized as one of the main pathological characteristics in the brain of Alzheimer's disease (AD), the effective strategies against Aβ neurotoxicity are still deficient up to now. Glucagon-like peptide 1 (GLP-1), a natural gut hormone, was found to be effective in modulating insulin signaling and neural protection, but short half-life limited its clinical application in AD treatment. CJC-1131, a newly designed GLP-1 analogue with very longer half-life, has shown good effectiveness in the treatment of type 2 diabetes mellitus (T2DM)...
March 14, 2017: Behavioural Brain Research
https://www.readbyqxmd.com/read/28315301/metabolites-of-2-3-diketogulonate-delay-peroxidase-action-and-induce-non-enzymic-h2o2-generation-potential-roles-in-the-plant-cell-wall
#15
Anna Kärkönen, Rebecca A Dewhirst, C Logan Mackay, Stephen C Fry
A proportion of the plant's l-ascorbate (vitamin C) occurs in the apoplast, where it and its metabolites may act as pro-oxidants and anti-oxidants. One ascorbate metabolite is 2,3-diketogulonate (DKG), preparations of which can non-enzymically generate H2O2 and delay peroxidase action on aromatic substrates. As DKG itself generates several by-products, we characterised these and their ability to generate H2O2 and delay peroxidase action. DKG preparations rapidly produced a by-product, compound (1), with λmax 271 and 251 nm at neutral and acidic pH respectively...
March 14, 2017: Archives of Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28304380/comprehensive-analysis-of-the-cancer-genome-atlas-reveals-a-unique-gene-and-non-coding-rna-signature-of-fibrolamellar-carcinoma
#16
Timothy A Dinh, Eva C M Vitucci, Eliane Wauthier, Rondell P Graham, Wendy A Pitman, Tsunekazu Oikawa, Mengjie Chen, Grace O Silva, Kevin G Greene, Michael S Torbenson, Lola M Reid, Praveen Sethupathy
Fibrolamellar carcinoma (FLC) is a unique liver cancer primarily affecting young adults and characterized by a fusion event between DNAJB1 and PRKACA. By analyzing RNA-sequencing data from The Cancer Genome Atlas (TCGA) for >9,100 tumors across ~30 cancer types, we show that the DNAJB1-PRKACA fusion is specific to FLCs. We demonstrate that FLC tumors (n = 6) exhibit distinct messenger RNA (mRNA) and long intergenic non-coding RNA (lincRNA) profiles compared to hepatocellular carcinoma (n = 263) and cholangiocarcinoma (n = 36), the two most common liver cancers...
March 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28302905/protein-kinase-a-regulates-the-ras-rap1-and-torc2-pathways-in-response-to-the-chemoattractant-camp-in-dictyostelium
#17
Margarethakay Scavello, Alexandra R Petlick, Ramya Ramesh, Valery F Thompson, Pouya Lotfi, Pascale G Charest
Efficient directed migration requires tight regulation of chemoattractant signal transduction pathways in both space and time, but the mechanisms involved in such regulation are not well understood. Here, we investigated the role of Protein Kinase A (PKA) in controlling signaling of the chemoattractant cAMP in Dictyostelium We found that cells lacking PKA display severe chemotaxis defects, including impaired directional sensing. Although PKA is an important regulator of developmental gene expression, including the cAMP receptor cAR1, our studies using exogenously expressed cAR1 in cells lacking PKA, cells lacking adenylyl cyclase A (ACA), and cells treated with the PKA-selective pharmacological inhibitor H89, suggest that PKA controls chemoattractant signal transduction, in part, through the regulation of RasG, Rap1, and TORC2...
March 16, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28302719/a-repressive-role-of-enhancer-of-zeste-homolog-2-in-11%C3%AE-hydroxysteroid-dehydrogenase-type-2-expression-in-human-placenta
#18
Rujuan Zuo, Xiaohui Liu, Wangsheng Wang, Wenjiao Li, Hao Ying, Kang Sun
The expression of 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2), which acts as a placental glucocorticoid barrier, is silenced in the cytotrophoblasts but substantially up-regulated during syncytialization. However, the repressive mechanism of 11β-HSD2 expression before syncytialization and how this repression is lifted during syncytialization remain mostly unresolved. Here we found that enhancer of zeste homolog 2 (EZH2) accounts for the silence of 11β-HSD2 expression via trimethylation of histone H3 lysine 27 (H3K27me3) at the promoter of 11β-HSD2 gene...
March 16, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28300612/characterization-of-melanin-concentrating-hormone-mch-and-its-receptor-in-chickens-tissue-expression-functional-analysis-and-fasting-induced-up-regulation-of-hypothalamic-mch-expression
#19
Lin Cui, Chan Lv, Jiannan Zhang, Chunheng Mo, Dongliang Lin, Juan Li, Yajun Wang
Melanin-concentrating hormone (MCH) is a neuropeptide expressed in the brain and exerts its actions through interaction with the two known G protein-coupled receptors, namely melanin-concentrating hormone receptor 1 and 2 (MCHR1 and MCHR2) in mammals. However, the information regarding the expression and functionality of MCH and MCHR(s) remains largely unknown in birds. In this study, using RT-PCR and RACE PCR, we amplified and cloned a MCHR1-like receptor, which is named cMCHR4 according to its evolutionary origin, and a MCHR2 from chicken brain...
March 11, 2017: Gene
https://www.readbyqxmd.com/read/28299836/involvement-of-pka-signalling-in-anti-inflammatory-effects-of-chitosan-oligosaccharides-in-ipec-j2-porcine-epithelial-cells
#20
J W Yang, G Tian, D W Chen, Y Yao, J He, P Zheng, X B Mao, J Yu, Z Q Huang, B Yu
Weaning is characterized by intestinal inflammation, which is a big challenge in pig industry. Control of intestinal inflammation is important for improvement of growth performance and health. Therefore, the study was focused on the anti-inflammatory activity of low-molecular-weight chitosan oligosaccharide (LCOS) in a porcine small intestinal epithelial cell line (IPEC-J2). The results showed that TNF-α, as inflammation inducer, significantly upregulated the mRNA expression of IL-8 and MCP-1. Afterwards, LCOS significantly attenuated mRNA expression of IL-8 and MCP-1 induced by TNF-α in the cells...
March 16, 2017: Journal of Animal Physiology and Animal Nutrition
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