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Journal of Receptor and Signal Transduction Research

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January 23, 2017: Journal of Receptor and Signal Transduction Research
Anshita Gupta, Chanchal Deep Kaur, Shailendra Saraf, Swarnlata Saraf
Targeted drug delivery through folate receptor (FR) has emerged as a most biocompatible, target oriented, and non-immunogenic cargoes for the delivery of anticancer drugs. FRs are highly overexpressed in many tumor cells (like ovarian, lung, breast, kidney, brain, endometrial, and colon cancer), and targeting them through conjugates bearing specific ligand with encapsulated nanodrug moiety is undoubtedly, a promising approach toward tumor targeting. Folate, being an endogenous ligand, can be exploited well to affect various cellular events occurring during the progress of tumor, in a more natural and definite way...
January 17, 2017: Journal of Receptor and Signal Transduction Research
Mohammad Reza Nourani, Hamideh Mahmoodzadeh Hosseini, Sadegh Azimzadeh Jamalkandi, Abbas Ali Imani Fooladi
CONTEXT: Mustard gas (e.g. sulfur mustard (SM)) has been used as a chemical agent in several battles and is still a potential worldwide menace. Besides local absorption, particularly in the skin, eyes and lungs, systemic spread of the agent also has detrimental effects on gonads, bone marrow and nervous system. Moreover, chronic exposure of SM to respiratory system causes death. Inducing oxidative stress, and disturbing DNA and tissue repair systems, inflammation and cell death signaling pathways have been introduced as molecular mechanisms of the injury...
April 2017: Journal of Receptor and Signal Transduction Research
Chun-Lin Chen, Deng-Chyang Wu, Min-Yun Liu, Ming-Wei Lin, Hung-Tu Huang, Yaw-Bin Huang, Li-Chai Chen, Yu-Yu Chen, Jih-Jung Chen, Pei-Hua Yang, Yu-Chen Kao, Pei-Yu Chen
PURPOSE: The transforming growth factor-beta (TGF-β) pathway is an important in the initiation and progression of cancer. Due to a strong association between an elevated colorectal cancer risk and increase fecal excretion of cholest-4-en-3-one, we aim to determine the effects of cholest-4-en-3-one on TGF-β signaling in the mink lung epithelial cells (Mv1Lu) and colorectal cancer cells (HT29) in vitro. METHODS: The inhibitory effects of cholest-4-en-3-one on TGF-β-induced Smad signaling, cell growth inhibition, and the subcellular localization of TGF-β receptors were investigated in epithelial cells using a Western blot analysis, luciferase reporter assays, DNA synthesis assay, confocal microscopy, and subcellular fractionation...
April 2017: Journal of Receptor and Signal Transduction Research
Cátia Sousa, Madalena Ribeiro, Ana Teresa Rufino, Alcino Jorge Leitão, Alexandrina Ferreira Mendes
CONTEXT/OBJECTIVE: Cell lines used to study the role of the G protein-coupled receptor 30 (GPR30) or G protein-coupled estrogen receptor (GPER) as a mediator of estrogen responses have yielded conflicting results. This work identified a simple assay to predict cell line competence for pharmacological studies of GPR30. MATERIALS AND METHODS: The phosphorylation or expression levels of ERK1/2, Akt, c-Fos and eNOS were evaluated to assess GPR30 activation in response to known agonists (17β-estradiol and G-1) in MCF-7 and T-47D breast cancer cell lines and in bovine aortic endothelial cells...
April 2017: Journal of Receptor and Signal Transduction Research
Shuyi Zhang, Lei Shi, Hongwen Ma, Hongzhou Li, Yanru Li, Ying Lu, Qiaoping Wang, Wen Li
Dihydroartemisinin (DHA), a semi-synthetic derivative of artemisinin, is associated with a broad range of biological properties including antitumor activity. However, the effect of DHA on gastric cancer has not been clearly clarified. The aim of this study was to investigate the role and mechanism of DHA in human gastric cancer cell line BGC-823. Cell viability was assessed by MTT assay. Cell apoptosis was analyzed with flow cytometry. The expressions of extracellular signal-regulated kinase (ERK), c-Jun N-terminal kinase (JNK), p38 mitogen-activated protein kinase (p38 MAPK) and their phosphorylated forms as well as apoptosis related proteins were examined by western blot analysis...
April 2017: Journal of Receptor and Signal Transduction Research
Guy Leclercq, Ioanna Laïos, Céline Elie-Caille, Denis Leiber, Guy Laurent, Eric Lesniewska, Zahra Tanfin, Yves Jacquot
Estrothiazine (ESTZ) is a weak estrogen sharing structural similarities with coumestrol. ESTZ failed to compete with [(3)H]17β-estradiol ([(3)H]17β-E2) for binding to the estrogen receptor α (ERα), questioning its ability to interact with the receptor. However, detection by atomic force spectroscopy (AFS) of an ESTZ-induced ERα dimerization has eliminated any remaining doubts. The effect of the compound on the proliferation of ERα-positive and negative breast cancer cells confirmed the requirement of the receptor...
April 2017: Journal of Receptor and Signal Transduction Research
M Kırça, N Oğuz, A Çetin, F Uzuner, A Yeşilkaya
Hyperuricemia and angiotensin II (Ang II) may have a pathogenetic role in the development of hypertension and atherosclerosis as well as cardiovascular disease (CVD) and its prognosis. The purpose of this study was to investigate whether uric acid can induce proliferative pathways of vascular smooth muscle cell (VSMC) that are thought to be responsible for the development of CVD. The phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK), p44/42 mitogen-activated protein kinase (p44/42 MAPK) and platelet-derived growth factor receptor β (PDGFRβ) was measured by Elisa and Western blot techniques to determine the activation of proliferative pathways in primary cultured VSMCs from rat aorta...
April 2017: Journal of Receptor and Signal Transduction Research
Fang Dong, Shu Yang, Haimei Sun, Jihong Yan, Xiaoxia Guo, Dandan Li, Deshan Zhou
Gastrointestinal (GI) distention is a common pathological characteristic in most GI motility disorders (GMDs), however, their detail mechanism remains unknown. In this study, we focused on Ca(2+) overload of smooth muscle, which is an early intracellular reaction to stretch, and its downstream MAPK signaling and also reduction of SCF in vivo and in vitro. We successfully established colonic dilation mouse model by keeping incomplete colon obstruction for 8 days. The results showed that persistent colonic dilation clearly induced Ca(2+) overload and activated all the three MAPK family members including JNK, ERK and p38 in smooth muscle tissues...
April 2017: Journal of Receptor and Signal Transduction Research
Angel Jemima Ebenezer, Prema Arunachalam, Berla Thangam Elden
CONTEXT: The histamine H4 receptor functionally expressed on human mast cells and their signaling pathways for the production of IL-13 and RANTES have never been analyzed side by side in a directly comparable manner. OBJECTIVE: Therefore, the aim of the study was to investigate signaling transduction pathways of H4R via ERK1/2, Akt and NFκB leading to the induction of inflammatory cytokine expression. MATERIALS AND METHODS: In the present study, HMC-1 cells and CBMCs were pretreated individually with H4R antagonist JNJ7777120, H1R antagonist mepyramine and signaling molecule inhibitors PD 98059, LY294002, Bay 117082 followed by stimulation was done with or without histamine or 4-MH...
April 2017: Journal of Receptor and Signal Transduction Research
Ting Shi, Robert S Papay, Dianne M Perez
The role of α1-adrenergic receptors (α1-ARs) and their subtypes in metabolism is not well known. Most previous studies were performed before the advent of transgenic mouse models and utilized transformed cell lines and poorly selective antagonists. We have now studied the metabolic regulation of the α1A- and α1B-AR subtypes in vivo using knock-out (KO) and transgenic mice that express a constitutively active mutant (CAM) form of the receptor, assessing subtype-selective functions. CAM mice increased glucose tolerance while KO mice display impaired glucose tolerance...
April 2017: Journal of Receptor and Signal Transduction Research
Thangaraj Sindhu, Pappu Srinivasan
Takeda G-protein-coupled receptor 5 (TGR5) is emerging as an important and promising target for the development of anti-diabetic drugs. Pharmacophore modeling and atom-based 3D-QSAR studies were carried out on a new series of 5-phenoxy-1,3-dimethyl-1H-pyrazole-4-carboxamides as highly potent agonists of TGR5. The generated best six featured pharmacophore model AAHHRR consists of two hydrogen bond acceptors (A): two hydrophobic groups (H) and two aromatic rings (R). The constructed 3D-QSAR model acquired excellent correlation coefficient value (R(2 )=( )0...
April 2017: Journal of Receptor and Signal Transduction Research
Neha Nagpal, Sukriti Goyal, Jaspreet Kaur Dhanjal, Liu Ye, Sunil C Kaul, Renu Wadhwa, Rupesh Chaturvedi, Abhinav Grover
INTRODUCTION: Cancer is one of the leading causes of mortality worldwide that requires attention in terms of extensive study and research. Eradication of mortalin-p53 interaction that leads to the inhibition of transcriptional activation or blocking of p53 from functioning as a suppressor and induction of nuclear translocation of p53 can prove to be one of the useful approaches for cancer management. RESULTS: In this study, we used structure-based approach to target the p53-binding domain of mortalin in order to prevent mortalin-p53 complex formation...
February 2017: Journal of Receptor and Signal Transduction Research
I-Shu Chen, Chiang-Ting Chou, Yuan-Yuarn Liu, Chia-Cheng Yu, Wei-Zhe Liang, Chun-Chi Kuo, Pochuen Shieh, Daih-Huang Kuo, Fu-An Chen, Chung-Ren Jan
Minoxidil is clinically used to prevent hair loss. However, its effect on Ca(2+) homeostasis in prostate cancer cells is unclear. This study explored the effect of minoxidil on cytosolic-free Ca(2+) levels ([Ca(2+)]i) and cell viability in PC3 human prostate cancer cells. Minoxidil at concentrations between 200 and 800 μM evoked [Ca(2+)]i rises in a concentration-dependent manner. This Ca(2+) signal was inhibited by 60% by removal of extracellular Ca(2+). Minoxidil-induced Ca(2+) influx was confirmed by Mn(2+)-induced quench of fura-2 fluorescence...
February 2017: Journal of Receptor and Signal Transduction Research
Peng Hu, Xun Xia, Qiang Xuan, Bao Yu Huang, Si Yan Liu, Dong Dong Zhang, Guang Mei Jiang, Yao Xu, Yuan Han Qin
The initiation and progression of renal interstitial fibrosis (RIF) is a complicated process in which many factors may play an activate role. Among these factors, C-type natriuretic peptide (CNP) is an endothelium-derived hormone and acts in a local, paracrine fashion to regulate vascular smooth muscle tone and proliferation. In this study, we established a rat model of unilateral ureteral obstruction (UUO). CNP expression tends to be higher immediately after ligation and declined at later time points, occurring predominantly in tubular epithelial cells...
February 2017: Journal of Receptor and Signal Transduction Research
Rajan Kumar Pandey, Bajarang Vasant Kumbhar, Shyam Sundar, Ambarish Kunwar, Vijay Kumar Prajapati
Visceral leishmaniasis (VL) is the most fatal form of leishmaniasis and it affects 70 countries worldwide. Increasing drug resistant for antileishmanial drugs such as miltefosine, sodium stibogluconate and pentamidine has been reported in the VL endemic region. Amphotericin B has shown potential antileishmanial activity in different formulations but its cost of treatment and associated nephrotoxicity have limited its use by affected people living in the endemic zone. To control the VL infection in the affected countries, it is necessary to develop new antileishmanial compounds with high efficacy and negligible toxicity...
February 2017: Journal of Receptor and Signal Transduction Research
Mahesh Ramalingam, Sung-Jin Kim
Parkinson's disease (PD) is the second most common neurodegenerative disorder after Alzheimer's disease (AD) associated with mitochondrial dysfunction mediated by oxidative stress. Astrocytes regulate neuronal function via the modulation of synaptic transmission and plasticity, secretion of growth factors, uptake of neurotransmitters, and regulation of extracellular ion concentrations and metabolic support of neurons. Therefore, this study was undertaken to investigate the mechanism of action of insulin on a 1-methyl-4-phenylpyridinium (MPP(+))-induced toxicity of events associated in cell viability and toxicity to the expression profile of cell signaling pathway proteins and genes in rat C6 glial cells...
February 2017: Journal of Receptor and Signal Transduction Research
Fengyun Wang, Yang Liu, Zhenyu Bi
OBJECTIVES: We aimed to study the antitumor effects of the PPARγ agonist pioglitazone on human retinoblastoma. METHODS: The effects of pioglitazone on cell proliferation and apoptosis of the human retinoblastoma Y79 cells were investigated by MTT assay and Hoechst 33258 staining assay. The apoptosis related protein levels were detected by western blot. Inflammationary factors analysis was evaluated by western blot and ELISA. The effect of pioglitazone on nuclear factor-kappa B (NF-κB)-dependent reporter gene transcription induced by LPS was analyzed by NF-κB-luciferase assay...
February 2017: Journal of Receptor and Signal Transduction Research
K Anbarasu, S Jayanthi
Estrogen receptor-α (ERα) is expressed more in patients with breast cancer and its level correlated with endocrine resistance. LMTK3 is reported as breast cancer target with regulation of estrogen receptor-α (ERα) through phosphorylation. In this computational study, structure-based inhibitor screening was performed on human LMTK3 using ZINC database. ATP-binding cavity with critical residues involved in the LMTK3 phosphorylation was used as target site for the screening. From the large ligand library, the best compounds were screen with three-phase virtual screening methods in Dockblaster, AutoDock Vina and AutoDock, respectively...
February 2017: Journal of Receptor and Signal Transduction Research
Pallavi Mohanty, Sonika Bhatnagar
The focal adhesion targeting (FAT) domain of focal adhesion kinase (FAK) exists in monomeric closed (c) or arm exchanged (ae) dimeric state. FAT interaction with Grb2 necessitates an intermediate open (o) state that interacts with Grb2 and activates signaling pathways leading to pathological cardiac hypertrophy. Targeted molecular dynamics (TMD) simulation was carried out in order to capture the structure of the intermediate formed by opening of Helix1 (H1) from monomeric cFAT leading to the formation of monomeric aeFAT...
February 2017: Journal of Receptor and Signal Transduction Research
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