Journal of receptor and signal transduction research最新文献

{"title":"p38 Mitogen-activated protein kinase accelerates emphysema in mouse model of chronic obstructive pulmonary disease.","authors":"Hiroyuki Amano,&nbsp;Kazuya Murata,&nbsp;Hirofumi Matsunaga,&nbsp;Kensuke Tanaka,&nbsp;Kento Yoshioka,&nbsp;Takeshi Kobayashi,&nbsp;Junji Ishida,&nbsp;Akiyoshi Fukamizu,&nbsp;Fumihiro Sugiyama,&nbsp;Tatsuhiko Sudo,&nbsp;Sadao Kimura,&nbsp;Koichiro Tatsumi,&nbsp;Yoshitoshi Kasuya","doi":"10.3109/10799893.2014.896380","DOIUrl":"https://doi.org/10.3109/10799893.2014.896380","url":null,"abstract":"<p><strong>Context: </strong>There are few short-term mouse models of chronic obstructive pulmonary disease (COPD) mimicking the human disease. In addition, p38 is recently recognized as a target for the treatment of COPD. However, the precise mechanism how p38 contributes to the pathogenesis of COPD is still unknown.</p><p><strong>Objective: </strong>We attempted to create a new mouse model for COPD by intra-tracheal administration of a mixture of lipopolysaccharide (LPS) and cigarette smoke solution (CSS), and investigated the importance of the p38 mitogen-activated protein kinase (p38) pathway in the pathogenesis of COPD.</p><p><strong>Methods: </strong>Mice were administered LPS + CSS once a day on days 0-4 and 7-11. Thereafter, CSS alone was administered to mice once a day on days 14-18. On day 28, histopathological changes of the lung were evaluated, and bronchoalveolar lavage fluid (BALF) was subjected to western blot array for cytokines. Transgenic (TG) mice expressing a constitutive-active form of MKK6, a p38-specific activator in the lung, were subjected to our experimental protocol of COPD model.</p><p><strong>Results: </strong>LPS + CSS administration induced enlargement of alveolar air spaces and destruction of lung parenchyma. BALF analyses of the LPS + CSS group revealed an increase in expression levels of several cytokines involved in the pathogenesis of human COPD. These results suggest that our experimental protocol can induce COPD in mice. Likewise, histopathological findings of the lung and induction of cytokines in BALF from MKK6 c.a.-TG mice were more marked than those in WT mice.</p><p><strong>Conclusion: </strong>In a new experimental COPD mouse model, p38 accelerates the development of emphysema.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"299-306"},"PeriodicalIF":2.8,"publicationDate":"2014-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2014.896380","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40281983","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genetic variants of synaptic vesicle and presynaptic plasma membrane proteins in idiopathic generalized epilepsy.","authors":"Mustafa Yilmaz,&nbsp;Tuba Gokdogan Edgunlu,&nbsp;Nigar Yilmaz,&nbsp;Esin Sakalli Cetin,&nbsp;Sevim Karakas Celik,&nbsp;Gülser Karadaban Emir,&nbsp;Ayşe Sözen","doi":"10.3109/10799893.2013.848893","DOIUrl":"https://doi.org/10.3109/10799893.2013.848893","url":null,"abstract":"<p><strong>Background: </strong>The aim of this study was to analyze the role of the genetic variants of two synaptic vesicle proteins (VAMP2 and Synaptotagmin XI) and two presynaptic plasma membrane proteins (Syntaxin 1A and SNAP-25) in patients with idiopathic generalized epilepsy (IGE).</p><p><strong>Method: </strong>Eighty-five patients with IGE and 93 healthy subjects were included in the study. We analyzed the functional polymorphisms of VAMP2, Synaptotagmin XI, Syntaxin 1A and SNAP-25 genes with polymerase chain reaction and restriction fragment length polymorphism methods.</p><p><strong>Results: </strong>In the patients with IGE, significant differences alleles and genotypes of 26 bp Ins/Del polymorphism of the VAMP2 gene and the 33-bp promoter region of Synaptotagmin XI were observed, however no associaton was found regarding Intron 7 rs1569061 of Syntaxin 1A gene, MnlI rs3746544 and DdeI rs1051312 polymorphisms of SNAP-25 gene compared with healthy subjects. Carriers of the C allele of Synaptotagmin XI had worse measures compared with the T allele of Synaptotagmin XI. In the haplotype analysis, the frequency of the T alleles of rs1569061 and of the C alleles of the 33-bp promoter region of Synaptotagmin XI was found to be significantly higher in patients with IGE as compared with the healthy subjects.</p><p><strong>Conclusion: </strong>The genetic variations of VAMP2, Synaptotagmin XI might be indication of the relationship between these genes and IGE.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"38-43"},"PeriodicalIF":2.8,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2013.848893","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40270157","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The signaling pathway of NADPH oxidase and its role in glomerular diseases.","authors":"Song Mao,&nbsp;Songming Huang","doi":"10.3109/10799893.2013.848892","DOIUrl":"https://doi.org/10.3109/10799893.2013.848892","url":null,"abstract":"<p><p>Nicotinamide adenine dinucleotide phosphate (NADPH) oxidase (Nox), a major source of reactive oxygen species, is a critical mediator of redox signaling. It is well-documented that oxidative stress is associated with the development of glomerular diseases (GN). Hence, the Nox was also thought to be involved in the pathogenesis of GN. However, the expression of Nox in various GN was not consistent, the mechanisms by which the activity of the Nox enzymes in regulating renal cells remains unclear. Signaling pathways might be very important in the pathogenesis of GN. We performed this review to provide a relatively complete signaling pathways flowchart for Nox to the investigators who were interested in the role of Nox in the pathogenesis of GN. Here, we reviewed the signal transduction pathway of Nox and its role in the pathogenesis of GN.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"6-11"},"PeriodicalIF":2.8,"publicationDate":"2014-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2013.848892","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40263063","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measurement of G protein-coupled receptor surface expression.","authors":"Pieter Beerepoot,&nbsp;Vincent M Lam,&nbsp;Ali Salahpour","doi":"10.3109/10799893.2013.781625","DOIUrl":"https://doi.org/10.3109/10799893.2013.781625","url":null,"abstract":"Abstract The quantity of G protein-coupled receptors (GPCRs) expressed on the cell surface is an important factor regulating receptor signaling. Maturation, internalization, recycling and degradation together determine the net amount of receptor surface expression. Understanding every aspect of the receptor lifecycle will facilitate the development of therapeutic applications. A number of assays for measuring the surface expression of GPCRs are currently available. This minireview summarizes the currently available assays and their suitability and usage for measuring GPCR surface expression.","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"162-5"},"PeriodicalIF":2.8,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2013.781625","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40246300","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A macromolecular trafficking complex composed of β₂-adrenergic receptors, A-Kinase Anchoring Proteins and L-type calcium channels.","authors":"Robyn Flynn,&nbsp;Christophe Altier","doi":"10.3109/10799893.2013.782219","DOIUrl":"https://doi.org/10.3109/10799893.2013.782219","url":null,"abstract":"<p><p>Abstract Sympathetic modulation of cardiac L-type calcium channels is an important mechanism for regulating heart rate and cardiac contractility. At the molecular level, activation of β-adrenergic receptors (βAR) increases calcium influx into cardiac myocytes by activating protein kinase A (PKA), leading to subsequent phosphorylation of L-type calcium channels. In the case of the β2AR, this process is facilitated by the presence of A-Kinase Anchoring Proteins (AKAPs) that serve as scaffolding proteins for the L-type calcium channel and the β2AR complex. Our work has shown that, in addition to facilitating PKA phosphorylation of the channel, AKAPs also promote an increase in the Cav1.2 channel surface expression. Here we review the molecular mechanisms of β2AR/AKAP/L-type channel interactions and trafficking.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"172-6"},"PeriodicalIF":2.8,"publicationDate":"2013-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2013.782219","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40247028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"EGFR overexpression relates to triple negative profile and poor prognosis in breast cancer patients in Tunisia.","authors":"Imen Kallel,&nbsp;Abdelmajid Khabir,&nbsp;Noureddine Boujelbene,&nbsp;Raoudha Abdennadher,&nbsp;Jamel Daoud,&nbsp;Mounir Frikha,&nbsp;Sami Aifa,&nbsp;Tahya Sallemi-Boudawara,&nbsp;Ahmed Rebaï","doi":"10.3109/10799893.2012.664552","DOIUrl":"https://doi.org/10.3109/10799893.2012.664552","url":null,"abstract":"<p><strong>Background: </strong>The prognosis of breast carcinoma is related to a large variety of clinical and pathological factors. Currently, only oestrogen (ER) and progesterone (PR) receptors and human epidermal growth factor receptor 2 (HER2) are used in routine pathological assessment as biomarkers. The aim of this study was to evaluate the prognostic impact of epidermal growth factor receptor (EGFR) expression individually and in combination to classical biomarkers (HER2, ER, and PR), and its relation to tumors with triple negative profile in Tunisian breast carcinoma.</p><p><strong>Methods: </strong>Immunohistochemistry was used to estimate the rate expression of these receptors. Univariate and multivariate analyses were used to explore the prognostic significance of EGFR in this study.</p><p><strong>Results: </strong>The expression rate of EGFR was 28.6%. EGFR expression was inversely correlated to that of ER (P < 0.001). Significant correlations between the expression of EGFR and the high histological Scarff-Bloom-Richardson (SBR) grade (P = 0.038) and also with tumors size (P = 0.041) were observed. The triple negative profile (TN: ER-/PR-/HER2-) was present in 17.3% of cases. EGFR overexpression was positively associated with this clinical aggressive profile (P < 0.001). Survival analysis showed that EGFR expression was associated with poor survival of patients (P = 0.004). In multivariate analysis, EGFR expression (P = 0.035) was found to be independent prognostic factors (significantly correlated to survival).</p><p><strong>Conclusion: </strong>EGFR overexpression was observed in 28.6% of Tunisian breast carcinoma, associated with unfavorable prognosis and with triple negative tumors. Systemically evaluation of EGFR in breast carcinoma could benefit especially to TN subgroup from EGFR targeting agents.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"142-9"},"PeriodicalIF":2.8,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2012.664552","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40144452","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"TGFBR1 mutations associated with Loeys-Dietz syndrome are inactivating.","authors":"Sarah Cardoso,&nbsp;Stephen P Robertson,&nbsp;Philip B Daniel","doi":"10.3109/10799893.2012.664553","DOIUrl":"https://doi.org/10.3109/10799893.2012.664553","url":null,"abstract":"<p><p>To assess the effect of Loeys-Dietz syndrome (LDS) mutations affecting TGFΒR1 a selection of seven disease-associated amino acid substitutions were introduced into wild type TGFβR1 and constitutively active TGFβR1(T204D). Receptor function was tested by co-transfection with a luciferase reporter or EGFP-tagged SMAD2 in HEK293 cells. All of the mutations were found to be inactivating for canonical TGF-β signaling. Differences in residual activity were not found to correlate with disease subtype. In co-transfection experiments with equal amounts wild-type receptor, the LDS mutations were found to confer a modest dominant negative effect. These results are discussed in relation to LDS and the related Marfan syndrome.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"150-5"},"PeriodicalIF":2.8,"publicationDate":"2012-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2012.664553","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40161810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Analyzing the responses of saccharin in context with melatonin receptors on the melanophores of the fish Labeo rohita (Ham.).","authors":"M D Mubashshir,&nbsp;Fraz Ahmed,&nbsp;Safia Sumoona,&nbsp;Mohd Ovais","doi":"10.3109/10799893.2012.660533","DOIUrl":"https://doi.org/10.3109/10799893.2012.660533","url":null,"abstract":"<p><p>The hormone melatonin regulates the biological clock and assist in various other physiologies of vertebrates. Present work is intended to check the affinity of saccharin towards the melatonin receptors and the possible role of saccharin interference in the melatonin physiology. The present in vitro study is based on the working model of isolated scale melanophores in the dorso-lateral region of Labeo rohita. The pigment cells were incubated in the agonist and the antagonists within a limited time frame and subsequently their Melanophore Size Index (MSI) were calculated. The inferences were drafted through the observed signal transduction upshots in pigment translocations within the melanophores. Saccharin, in a wide dose range, has consistently induced a concentration-related aggregation similar to the aggregatory effect as shown by melatonin on the melanophores. Binding of saccharin with the receptors and eliciting its aggregatory effect is partially dependent on the release of neurotransmitters. The aggregatory effects were found to be significantly blocked by luzindole, K185, and prazosin, which are the potent melatonin receptor blockers, at the higher concentrations of saccharin. Hence, all the three subtypes of melatonin receptors viz. MT₁, MT₂, and MT₃ are participating in saccharin-mediated aggregations. Blocking by neomycin shows that Ca²⁺ ions are very crucial in dispensing the aggregatory effect of the sweetener. This research demands that an intensive and careful thorough study should be made about saccharin, specifically its effects upon melatonin physiology, before its unwarranted use as the food ingredients for human use.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"114-9"},"PeriodicalIF":2.8,"publicationDate":"2012-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2012.660533","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40152982","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Reversal of hemorrhagic shock in rats using the metabolically stable thyrotropin-releasing hormone analog taltirelin hydrate.","authors":"Hidetoshi Asai,&nbsp;Yumi Watanabe,&nbsp;Rikako Yamauchi-Kohno,&nbsp;Osamu Doi","doi":"10.3109/10799893.2011.625427","DOIUrl":"https://doi.org/10.3109/10799893.2011.625427","url":null,"abstract":"<p><p>We investigated the effect of taltirelin hydrate ((−)-N-[(S)-hexahydro-1-methyl- 2,6-dioxo-4-pyrimidinyl-carbonyl]-L-histidyl-L-prolinamide tetrahydrate; taltirelin), a metabolically stable thyrotropin-releasing hormone (TRH) analog, on circulatory function, respiratory function, and viable time after bleeding in urethane-anesthetized rats. Massive volume-controlled bleeding caused marked reductions in mean arterial pressure (MAP) and respiratory rate (RR). The vital signs of control rats were lost within an average of 23 min after bleeding. Intravenous administration of taltirelin (0.03−0.3 mg/kg) and TRH (1 and 3 mg/kg) immediately after bleeding accelerated recovery of MAP and RR, and prolonged viable time in a dose-dependent manner. The potency of taltirelin in accelerating MAP and RR recovery and prolonging viable time was higher when compared with that of TRH. In addition, recovery of MAP and RR and the extension of viable time by taltirelin were inhibited by preintraperitoneal administration of atropine sulfate, which is a centrally acting muscarinic antagonist, but not by that of atropine methylbromide, which is a peripherally acting muscarinic antagonist. Taltirelin also recovered decreased arterial pH, bicarbonate ions, and base excess, and prevented a decrease in arterial oxygen saturation. In conclusion, the anti-shock effect of taltirelin was more potent than that of TRH. Taltirelin activity was mediated by the central muscarinic cholinergic system. In addition, taltirelin also corrected metabolic acidosis. These results suggest that taltirelin could be useful in the treatment of hypovolemic shock.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"416-22"},"PeriodicalIF":2.8,"publicationDate":"2011-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2011.625427","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40121448","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Receptor tyrosine kinases: from biology to pathology.","authors":"Mouna Choura,&nbsp;Ahmed Rebaï","doi":"10.3109/10799893.2011.625425","DOIUrl":"https://doi.org/10.3109/10799893.2011.625425","url":null,"abstract":"<p><p>Receptor tyrosine kinases (RTKs) are transmembrane proteins involved in the control of fundamental cellular processes in metazoans. RTKs possess a general structure that includes an extracellular domain, a transmembrane domain and a highly conserved tyrosine kinase domain. RTKs are classified according to their variable extracellular ligand-binding domain. Studies of human RTK members have yielded a wealth of information elucidating their importance. Improper functioning of these enzymes due to mutations, mainly in the kinase domain, is often manifested in various human diseases and is known to be involved in several types of cancer. Here we summarize most of human RTKs, their cognate ligands, as well as related diseases and discuss the eventual use of certain RTKs as new therapeutic targets.</p>","PeriodicalId":520688,"journal":{"name":"Journal of receptor and signal transduction research","volume":" ","pages":"387-94"},"PeriodicalIF":2.8,"publicationDate":"2011-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.3109/10799893.2011.625425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40116305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}