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Xue Jiang, Yawen Zhou, Kelvin K L Wu, Zhanrui Chen, Aimin Xu, Kenneth K Y Cheng
AIMS/HYPOTHESIS: Beta cell inflammation and demise is a feature of type 1 diabetes. The insulin-sensitising molecule 'adaptor protein, phosphotyrosine interacting with PH domain and leucine zipper 1' (APPL1), which contains an NH2-terminal Bin/Amphiphysin/Rvs domain, a central pleckstrin homology domain and a COOH-terminal phosphotyrosine-binding domain, has been shown to modulate inflammatory response in various cell types but its role in regulating beta cell mass and inflammation in type 1 diabetes remains unknown...
December 23, 2016: Diabetologia
Anja Zeigerer, Anne Wuttke, Giovanni Marsico, Sarah Seifert, Yannis Kalaidzidis, Marino Zerial
Exploring the cell biology of hepatocytes in vitro could be a powerful strategy to dissect the molecular mechanisms underlying the structure and function of the liver in vivo. However, this approach relies on appropriate in vitro cell culture systems that can recapitulate the cell biological and metabolic features of the hepatocytes in the liver whilst being accessible to experimental manipulations. Here, we adapted protocols for high-resolution fluorescence microscopy and quantitative image analysis to compare two primary hepatocyte culture systems, monolayer and collagen sandwich, with respect to the distribution of two distinct populations of early endosomes (APPL1 and EEA1-positive), endocytic capacity, metabolic and signaling activities...
January 1, 2017: Experimental Cell Research
Youming Ding, Yingkang Cao, Bin Wang, Lei Wang, Yemin Zhang, Deling Zhang, Xiaoyan Chen, Mingxin Li, Changhua Wang
Leptin has been implicated in tumorigenesis and tumor progression, particularly in obese patients. As a multifunctional adaptor protein, APPL1 (containing pleckstrin homology domain, phosphotyrosine binding domain, and a leucine zipper motif 1) plays a critical role in regulating adiponectin and insulin signaling pathways. Currently, high APPL1 level has been suggested to be related to metastases and progression of some types of cancer. However, the intercourse between leptin signaling pathway and APPL1 remains poorly understood...
2016: PloS One
Michelangela Barbieri, Raffaele Marfella, Antonietta Esposito, Maria Rosaria Rizzo, Edith Angellotti, Ciro Mauro, Mario Siniscalchi, Fabio Chirico, Pasquale Caiazzo, Fulvio Furbatto, Alessandro Bellis, Nunzia D'Onofrio, Milena Vitiello, Franca Ferraraccio, Giuseppe Paolisso, Maria Luisa Balestrieri
AIMS: Glucagon like peptide 1 (GLP-1) analogues and dipeptidyl peptidase IV (DPP-4) inhibitors reduce atherosclerosis progression in type 2 diabetes mellitus (T2DM) patients and are associated with morphological and compositional characteristics of stable plaque phenotype. GLP-1 promotes the secretion of adiponectin which exerts anti-inflammatory effects through the adaptor protein PH domain and leucine zipper containing 1 (APPL1). The potential role of APPL1 expression in the evolution of atherosclerotic plaque in TDM2 patients has not previously evaluated...
October 5, 2016: Journal of Diabetes and its Complications
Sang-Jin Lee, Jeongmi Hwang, Hyeon-Ju Jeong, Miran Yoo, Ga-Yeon Go, Jae-Rin Lee, Young-Eun Leem, Jong Woo Park, Dong-Wan Seo, Yong Kee Kim, Myong-Joon Hahn, Jeung-Whan Han, Jong-Sun Kang, Gyu-Un Bae
Skeletal myogenesis is coordinated by multiple signaling pathways that control cell adhesion/migration, survival and differentiation accompanied by muscle-specific gene expression. A cell surface protein Cdo is involved in cell contact-mediated promyogenic signals through activation of p38MAPK and AKT. Protein kinase C-related kinase 2 (PKN2/PRK2) is implicated in regulation of various biological processes, including cell migration, adhesion and death. It has been shown to interact with and inhibit AKT thereby inducing cell death...
October 20, 2016: Cell Death & Disease
Yi Wang, Kenneth K Y Cheng, Karen S L Lam, Donghai Wu, Yu Wang, Yu Huang, Paul M Vanhoutte, Gary Sweeney, Yiming Li, Aimin Xu
No abstract text is available yet for this article.
October 2016: Diabetes
Kenneth K Y Cheng, Karen S L Lam, Yu Wang, Yu Huang, David Carling, Donghai Wu, Chiwai Wong, Aimin Xu
No abstract text is available yet for this article.
October 2016: Diabetes
Caroline Gastebois, Clément Villars, Jocelyne Drai, Emmanuelle Canet-Soulas, Stéphane Blanc, Audrey Bergouignan, Etienne Lefai, Chantal Simon
PURPOSE: To delineate the direct effect of physical activity on adiponectin metabolism, we investigated the impact of contrasted physical activity changes, independent of body mass changes, on adiponectin plasma concentration and muscle sensitivity in lean and overweight adult males. METHODS: Eleven physically active lean men (70.6 ± 2.1 kg) were subjected to 1-month detraining; 9 sedentary lean men (73.1 ± 3.3 kg); and 11 sedentary overweight men (97.5 ± 3...
December 2016: European Journal of Applied Physiology
Lorena Oróstica, Carlos Rosas, Francisca Plaza-Parrochia, Isis Astorga, Fernando Gabler, Víctor García, Carmen Romero, Margarita Vega
BACKGROUND: Polycystic Ovary Syndrome (PCOS) is a prevalent endocrine/ metabolic disorder characterized by hyperandrogenemia and in most cases, by hyperinsulinemia in addition to obesity. Besides ovarian dysfunction, endometrial physiology is also disrupted since this tissue is highly dependent on the action of steroids; in case of conception cycles, high percentage of abortion is observed. Because of the endocrine/metabolic alterations, PCOS-women present high probability to develop hyperplasia and endometrial cancer, where an imbalance of cell proliferation/apoptosis processes is detected...
2016: Current Pharmaceutical Design
Ali Jason Saleh, Bahram M Soltani, Sadat Dokanehiifard, Abdallah Medlej, Mahmoud Tavalaei, Seyed Javad Mowla
PI3K/AKT signaling is involved in cell survival, proliferation, and migration. In this pathway, PI3Kα enzyme is composed of a regulatory protein encoded by p85 gene and a catalytic protein encoded by PIK3CA gene. Human PIK3CA locus is amplified in several cancers including lung and colorectal cancer (CRC). Therefore, microRNAs (miRNAs) that are encoded within the PIK3CA gene might have a role in cancer development. Here, we report a novel microRNA named PIK3CA-miR1 (EBI accession no. LN626315), which is located within PIK3CA gene...
October 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Tsugumichi Saito, Shuichi Okada, Yoko Shimoda, Yuko Tagaya, Aya Osaki, Eijiro Yamada, Ryo Shibusawa, Yasuyo Nakajima, Atsushi Ozawa, Tetsurou Satoh, Masatomo Mori, Masanobu Yamada
Expression of adaptor protein, phosphotyrosine interaction, pleckstrin homology domain, and leucine zipper containing 1 (APPL1) promoted glucose transporter 4 (GLUT4) translocation and glucose uptake in adipose and muscle tissues in response to stimulation with insulin, adiponectin, or exercise. In response to mechanical stretch, knockdown of APPL1 in C2C12 myotubes suppressed glucose uptake. APPL1-induced increased glucose uptake was mediated by protein kinase C (PKC) ζ but not AKT, AMPK, or calmodulin-dependent protein kinase...
November 2016: Cellular Signalling
R Dehghan, M Saidijam, M Mehdizadeh, N Shabab, M Yavangi, T Artimani
No abstract text is available yet for this article.
June 24, 2016: Journal of Endocrinological Investigation
Jiejie Wang, Wen Lu, Lin Chen, Ping Zhang, Tingting Qian, Wei Cao, Jianhong Luo
Accumulating evidence indicates that the synaptic activation of N-methyl-D-aspartate receptors (NMDARs) has a neuroprotective effect on neurons. Our previous study demonstrated that APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif) mediates the synaptic activity-dependent activation of PI3K-Akt signaling via coupling this pathway with NMDAR-PSD95 (postsynaptic density protein 95) complexes. However, the molecular mechanism underlying this process is still unknown...
August 2016: Neuroscience Bulletin
Mónica Fernández-Monreal, Carla Sánchez-Castillo, José A Esteban
Hippocampal synaptic plasticity involves both membrane trafficking events and intracellular signaling, but how these are coordinated is far from clear. The endosomal transport of glutamate receptors in and out of the postsynaptic membrane responds to multiple signaling cascades triggered by synaptic activity. In this work, we have identified adaptor protein containing a plekstrin homology domain, phosphotyrosine-binding domain and leucine zipper motif 1 (APPL1) as a crucial element linking trafficking and signaling during synaptic plasticity...
July 15, 2016: Journal of Cell Science
Youming Ding, Deling Zhang, Bin Wang, Yemin Zhang, Lei Wang, Xiaoyan Chen, Mingxin Li, Zhao Tang, Changhua Wang
Adiponectin has been shown to suppress hepatic gluconeogenesis. However, the signaling pathways underlying its action remain ill-defined. The purpose of this study was to examine the potential role of APPL1 in mediating anti-gluconeogenic ability of adiponectin. Primary hepatocytes were isolated from male C57BL/6 mice. Western blot and RT-PCR were performed to detect protein expression and mRNA level, respectively. The protein-protein association was determined by immunoprecipitation and GST pull-down assay...
September 15, 2016: Molecular and Cellular Endocrinology
Jeremy C Yeo, Adam A Wall, Lin Luo, Nicholas D Condon, Jennifer L Stow
Macrophages are activated by contact with pathogens to mount innate immune defenses against infection. Toll-like receptor 4 (TLR4) at the macrophage surface recognizes and binds bacterial lipopolysaccharide (LPS), setting off signaling and transcriptional events that lead to the secretion of pro- and anti-inflammatory cytokines; these in turn control inflammatory and antimicrobial responses. Although the complex regulatory pathways downstream of TLR4 have been extensively studied, further molecules critical for modulating the resulting cytokine outputs remain to be characterized...
September 2016: Traffic
Keith Dadson, Vera Kovacevic, Palanivel Rengasamy, Grace Ha Eun Kim, Stellar Boo, Ren-Ke Li, Isaac George, P Christian Schulze, Boris Hinz, Gary Sweeney
BACKGROUND: The cardiac remodelling process in advanced heart failure due to pressure overload has not been clearly defined but likely involves mechanisms of cardiac fibrosis and cardiomyocyte hypertrophy. The aim of this study was to examine pressure overload (PO)-induced cardiac remodelling processes and their reversibility after unloading in both humans with heart failure and a mouse model of PO induced by aortic constriction. METHODS & RESULTS: Speckle tracking echocardiography showed PO-induced cardiac dysfunction in mice was reversible after removal of aortic constriction to unload...
August 1, 2016: International Journal of Cardiology
J S Zhai, J G Song, C H Zhu, K Wu, Y Yao, N Li
BACKGROUND: Although appl1 is overexpressed in many cancers, its status in gastric cancer (gc) is not known. In the present study, we used relevant pathologic and clinical data to investigate appl1 expression in patients with gc. METHODS: In 47 gc and 27 non-gc surgical specimens, immunohistochemistry was used to detect the expression of appl1, and reverse-transcriptase polymerase chain reaction (rt-pcr) was used to detect messenger rna (mrna). A scatterplot visualized the relationship between survival time and mrna expression in gc patients...
April 2016: Current Oncology
R Dehghan, M Saidijam, M Mehdizade, N Shabab, M Yavangi, T Artimani
PURPOSE: To investigate the expression of Adaptor protein containing a PH domain, PTB domain and leucine zipper motif 1 (APPL1), insulin receptor (INSR), adiponectin and adiponectin receptors (adipoR1 and R2) and their possible associations in granulosa cells (GCs) of 22 polycystic ovary syndrome (PCOS) women compared to the 22 non-PCOS controls with normal ovulatory function matched for BMI (body mass index). METHODS: In this study, 44 infertile women aged 18-40 years undergoing in vitro fertilization (IVF) protocol were recruited...
September 2016: Journal of Endocrinological Investigation
Y Pu, H Wu, S Lu, H Hu, D Li, Y Wu, Z Tang
Human jaw bone marrow mesenchymal stem cells (h-JBMMSCs) are multipotent progenitor cells with osteogenic differentiation potential. The relationship between adiponectin (APN) and the metabolism of h-JBMMSCs has not been fully elucidated, and the underlying mechanism remains unclear. The aim of the study was to investigate the effect and mechanism of APN on h-JBMMSC metabolism. h-JBMMSCs were obtained from the primary culture of human jaw bones and treated with or without APN (1 µg/mL). Osteogenesis-related gene expression was evaluated by real-time polymerase chain reaction (PCR), alkaline phosphatase (ALP) activity assay, and enzyme-linked immunosorbent assay (ELISA)...
July 2016: Journal of Dental Research
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