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https://www.readbyqxmd.com/read/29741772/curcumin-alleviates-ischemia-reperfusion-induced-late-kidney-fibrosis-through-the-appl1-akt-signaling-pathway
#1
Chen Hongtao, Fan Youling, Huang Fang, Peng Huihua, Zhong Jiying, Zhou Jun
As a major cause of renal failure, transient renal ischemia and reperfusion induce both acute kidney injury and late fibrosis, which are the common pathological manifestations of end-stage renal disease. Curcumin is a biologically active polyphenolic compound found in turmeric. Increasing evidence has demonstrated that curcumin has a protective action against renal fibrosis, whereas mechanisms underlying the anti-fibrosis role of curcumin remain poorly defined. Here, we found that APPL1, an important intracellular binding partner for AdipoR, was involved in the pathogenesis of acute injury or fibrosis and was significantly upregulated by curcumin in a mouse model of ischemia reperfusion-induced late kidney fibrosis...
May 9, 2018: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29726111/clinical-usefulness-of-comprehensive-genetic-screening-in-mody-a-novel-abcc8-mutation-in-a-previously-screened-family
#2
Stephanie Robyn Johnson, Paul Leo, Louise Sonia Conwell, Mark Harris, Matthew Arthur Brown, Emma Letitia Duncan
Maturity-onset diabetes of the young (MODY) is the commonest form of monogenic diabetes, resulting from dominant mutations in one of fourteen genes that regulate beta-cell function (HNF4A, GCK, HNF1A, PDX1, HNF1B, NEUROD1, KLF11, CEL, PAX4, INS, BLK, ABCC8,KCNJ11 and APPL1 1,2 ). MODY accounts for 2-2.5% of childhood diabetes 3 , yet MODY genetic screening is uncommon, even in highly suggestive families, and when performed often limited to the commonest genes (e.g.HNF1A and GCK) 4 .
May 4, 2018: Journal of Diabetes
https://www.readbyqxmd.com/read/29705396/acute-physical-exercise-increases-the-adaptor-protein-appl1-in-the-hypothalamus-of-obese-mice
#3
Rafael Calais Gaspar, Vitor Rosetto Muñoz, Guilherme Pedron Formigari, Gabriel Keine Kuga, Susana Castelo Branco Ramos Nakandakari, José Diego Botezelli, Adelino S R da Silva, Dennys Esper Cintra, Leandro Pereira de Moura, Eduardo Rochete Ropelle, José Rodrigo Pauli
Adiponectin is considered an adipokine that has essential anti-inflammatory and insulin-sensitivity actions. The adaptor protein containing the pleckstrin homology domain, the phosphotyrosine-binding domain, and leucine zipper motif 1 (APPL1) is a protein involved in adiponectin signaling that plays a role in many physiological and pathophysiological processes. In the central nervous system, adiponectin can potentiate the effects of leptin in the arcuate proopiomelanocortin (POMC) neurons. However, the role of APPL1 in the hypothalamus is not well understood...
April 26, 2018: Cytokine
https://www.readbyqxmd.com/read/29611645/expression-of-follicle-stimulating-hormone-receptor-fshr-protein-kinase-b-2-akt2-and-adapter-protein-with-ph-domain-ptb-domain-and-leucine-zipper-appl1-in-pig-ovaries
#4
Ning Zhou, Ning Wang, Xiang Qin, Qian Liu, Juhua Wang, Hui Dong, Jie Zhou, Fugui Fang
Follicle-stimulating hormone (FSH) regulates oogenesis and spermatogenesis by binding to its receptor (FSHR) on target cells in the ovary and testis, respectively. The signaling cascades activated after ligand binding are extremely complex and have been shown to include protein kinase A and phosphatidylinositol 3-kinase/protein kinase. The adapter protein APPL1 (adapter protein with PH domain, PTB domain, and leucine zipper), which is an assortment of other signaling proteins, was previously identified to interact with the FSH receptor (FSHR) and the protein kinase B (AKT) pathway...
December 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/29523594/dual-inhibition-of-akt-mtor-and-ar-signaling-by-targeting-hdac3-in-pten-or-spop-mutated-prostate-cancer
#5
Yuqian Yan, Jian An, Yinhui Yang, Di Wu, Yang Bai, William Cao, Linlin Ma, Junhui Chen, Zhendong Yu, Yundong He, Xin Jin, Yunqian Pan, Tao Ma, Shangqian Wang, Xiaonan Hou, Saravut John Weroha, R Jeffrey Karnes, Jun Zhang, Jennifer J Westendorf, Liguo Wang, Yu Chen, Wanhai Xu, Runzhi Zhu, Dejie Wang, Haojie Huang
AKT-mTOR and androgen receptor (AR) signaling pathways are aberrantly activated in prostate cancer due to frequent PTEN deletions or SPOP mutations. A clinical barrier is that targeting one of them often activates the other. Here, we demonstrate that HDAC3 augments AKT phosphorylation in prostate cancer cells and its overexpression correlates with AKT phosphorylation in patient samples. HDAC3 facilitates lysine-63-chain polyubiquitination and phosphorylation of AKT, and this effect is mediated by AKT deacetylation at lysine 14 and 20 residues and HDAC3 interaction with the scaffold protein APPL1...
April 2018: EMBO Molecular Medicine
https://www.readbyqxmd.com/read/29486166/adiponectin-attenuates-neuronal-apoptosis-induced-by-hypoxia-ischemia-via-the-activation-of-adipor1-appl1-lkb1-ampk-pathway-in-neonatal-rats
#6
Ningbo Xu, Yixin Zhang, Desislava Met Doycheva, Yan Ding, Yiting Zhang, Jiping Tang, Hongbo Guo, John H Zhang
Adiponectin is an important adipocyte-derived plasma protein that has beneficial effects on cardio- and cerebrovascular diseases. A low level of plasma Adiponectin is associated with increased mortality post ischemic stroke; however, little is known about the causal role of Adiponectin as well as its molecular mechanisms in neonatal hypoxia ischemia (HI). In the present study, ten-day-old rat pups were subjected to right common carotid artery ligation followed by 2.5 h hypoxia. Recombinant human Adiponectin (rh-Adiponectin) was administered intranasally 1 h post HI...
May 1, 2018: Neuropharmacology
https://www.readbyqxmd.com/read/29483192/alternative-splicing-variant-of-the-scaffold-protein-appl1-suppresses-hepatic-adiponectin-signaling-and-function
#7
Amanda K Galan-Davila, Jiyoon Ryu, Kun Dong, Yang Xiao, Zhe Dai, Deling Zhang, Zhi Li, Amanda M Dick, Kevin D Liu, Amrita Kamat, Min Lu, Qunfeng Dong, Feng Liu, Lily Q Dong
Adiponectin is an adipocyte-derived hormone with antidiabetic activities that include increasing the sensitivity of cells to insulin. Adaptor protein containing pleckstrin homology domain, phosphotyrosine-binding domain, and leucine zipper motif (APPL1) stimulates adiponectin signaling and promotes adiponectin's insulin-sensitizing effects by binding to two adiponectin receptors, AdipoR1 and AdipoR2, and the insulin receptor. In this study, we report an alternative splicing variant of APPL1 (APPL1sv) that is highly expressed in mouse liver, pancreas, and spleen tissues...
April 20, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29406784/resistance-training-recovers-attenuated-appl1-expression-and-improves-insulin-induced-akt-signal-activation-in-skeletal-muscle-of-type-2-diabetic-rats
#8
Kohei Kido, Satoru Ato, Takumi Yokokawa, Koji Sato, Satoshi Fujita
Adapter protein containing PH domain, PTB domain, and leucine zipper motif 1 (APPL1) has been reported as a positive regulator of insulin-stimulated Akt activation. The expression of APPL1 is reduced in skeletal muscles of type 2 diabetic (T2D) animals, implying that APPL1 may be an important factor affecting insulin sensitivity. However, the regulation of APPL1 expression and the physiological interventions modulating these effects are unclear. Accordingly, we first confirmed that APPL1 expression and Akt phosphorylation were significantly attenuated in skeletal muscles of T2D rats...
February 6, 2018: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/29361527/%C3%AE-5%C3%AE-1-integrin-trafficking-and-rac-activation-are-regulated-by-appl1-in-a-rab5-dependent-manner-to-inhibit-cell-migration
#9
Nicole L Diggins, Hakmook Kang, Alissa Weaver, Donna J Webb
Cell migration is a tightly coordinated process that requires the spatiotemporal regulation of many molecular components. Because adaptor proteins can serve as integrators of cellular events, they are being increasingly studied as regulators of cell migration. The adaptor protein containing a pleckstrin-homology (PH) domain, phosphotyrosine binding (PTB) domain, and leucine zipper motif 1 (APPL1) is a 709 amino acid endosomal protein that plays a role in cell proliferation and survival as well as endosomal trafficking and signaling...
March 6, 2018: Journal of Cell Science
https://www.readbyqxmd.com/read/29212031/integration-of-gpcr-signaling-and-sorting-from-very-early-endosomes-via-opposing-appl1-mechanisms
#10
Silvia Sposini, Frederic G Jean-Alphonse, Mohammed A Ayoub, Affiong Oqua, Camilla West, Stuart Lavery, Jan J Brosens, Eric Reiter, Aylin C Hanyaloglu
Endocytic trafficking is a critical mechanism for cells to decode complex signaling pathways, including those activated by G-protein-coupled receptors (GPCRs). Heterogeneity in the endosomal network enables GPCR activity to be spatially restricted between early endosomes (EEs) and the recently discovered endosomal compartment, the very early endosome (VEE). However, the molecular machinery driving GPCR activity from the VEE is unknown. Using luteinizing hormone receptor (LHR) as a prototype GPCR for this compartment, along with additional VEE-localized GPCRs, we identify a role for the adaptor protein APPL1 in rapid recycling and endosomal cAMP signaling without impacting the EE-localized β2-adrenergic receptor...
December 5, 2017: Cell Reports
https://www.readbyqxmd.com/read/29021281/survival-of-brca2-deficient-cells-is-promoted-by-gipc3-a-novel-genetic-interactor-of-brca2
#11
Xia Ding, Subha Philip, Betty K Martin, Yan Pang, Sandra Burkett, Deborah A Swing, Chinmayi Pamala, Daniel A Ritt, Ming Zhou, Deborah K Morrison, Xinhua Ji, Shyam K Sharan
BRCA2 loss-of-heterozygosity (LOH) is frequently observed in BRCA2 -mutated tumors, but its biallelic loss causes embryonic lethality in mice and inhibits proliferation of normal somatic cells. Therefore, it remains unclear how loss of BRCA2 contributes to tumorigenesis. One possibility is that mutation in potential genetic interactors of BRCA2 , such as TRP53 , is required for cell survival/proliferation in the absence of BRCA2. In this study, using an insertional mutagenesis screen in mouse embryonic stem cells (mESC), we have identified GIPC3 (GAIP-interacting protein C-terminus 3) as a BRCA2 genetic interactor that contributes to survival of Brca2 -null mESC...
December 2017: Genetics
https://www.readbyqxmd.com/read/28946816/effect-of-tnf-%C3%AE-on-molecules-related-to-the-insulin-action-in-endometrial-cells-exposed-to-hyperandrogenic-and-hyperinsulinic-conditions-characteristics-of-polycystic-ovary-syndrome
#12
Lorena Oróstica, Paula García, Carolina Vera, Víctor García, Carmen Romero, Margarita Vega
Polycystic ovary syndrome (PCOS) affects not only ovarian functions but is also able to affect endometrium metabolism. Around 80% of women with PCOS are obese. High tumor necrosis factor (TNF)-α production and low adiponectin levels are characteristics of obesity. Interestingly, endometrium from obese women with PCOS presents an insulin-resistance condition, high TNF-α levels, and low adiponectin levels. However, TNF-α effect on molecules associated with insulin action in endometrial cells remains unclear...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28902365/appl1-promotes-the-migration-of-gastric-cancer-cells-by-regulating-akt2-phosphorylation
#13
Yingxun Liu, Chunli Zhang, Lingyu Zhao, Ning Du, Ni Hou, Tusheng Song, Chen Huang
As a multifunctional adaptor protein, APPL1 (adaptor protein containing pleckstrin homology domain, phosphotyrosine binding domain and a leucine zipper motif 1) is overexpressed in many cancers, and has been implicated in tumorigenesis and tumor progression. The present study investigated the expression of APPL1 in gastric carcinoma and the function in regulating cell migration. We investigated the expression of APPL1 in gastric carcinoma based upon The Cancer Genome Atlas (TCGA) database. The expression of APPL1 in collected gastric carcinoma tissues and cultured cells was measured by qRT-PCR and western blot analysis...
September 5, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28620038/appl1-is-a-multifunctional-endosomal-signaling-adaptor-protein
#14
REVIEW
Nicole L Diggins, Donna J Webb
Endosomal adaptor proteins are important regulators of signaling pathways underlying many biological processes. These adaptors can integrate signals from multiple pathways via localization to specific endosomal compartments, as well as through multiple protein-protein interactions. One such adaptor protein that has been implicated in regulating signaling pathways is the<u>a</u>daptor protein containing a<u>p</u>leckstrin homology (PH) domain,<u>p</u>hosphotyrosine-binding (PTB) domain, and<u>l</u>eucine zipper motif 1 (APPL1)...
June 15, 2017: Biochemical Society Transactions
https://www.readbyqxmd.com/read/28593738/sex-differences-in-the-regulation-of-porcine-coronary-artery-tone-by-perivascular-adipose-tissue-a-role-of-adiponectin
#15
Abdulla A Ahmad, Michael D Randall, Richard E Roberts
BACKGROUND AND PURPOSE: As there is sexual dimorphism in the regulation of vascular tone, the aim of this present study was to determine whether there are sex differences in perivascular adipose tissue (PVAT)-mediated regulation of the porcine coronary artery (PCA) tone. EXPERIMENTAL APPROACH: Isometric tension recording system was used to record changes in tone in PCAs. Western blot analysis was performed to examine the expression of adiponectin in PVAT and adiponectin receptors and adiponectin binding protein (APPL1) in PCA...
August 2017: British Journal of Pharmacology
https://www.readbyqxmd.com/read/28591580/myo6-regulates-spatial-organization-of-signaling-endosomes-driving-akt-activation-and-actin-dynamics
#16
Thomas A Masters, David A Tumbarello, Margarita V Chibalina, Folma Buss
APPL1- and RAB5-positive signaling endosomes play a crucial role in the activation of AKT in response to extracellular stimuli. Myosin VI (MYO6) and two of its cargo adaptor proteins, GIPC and TOM1/TOM1L2, localize to these peripheral endosomes and mediate endosome association with cortical actin filaments. Loss of MYO6 leads to the displacement of these endosomes from the cell cortex and accumulation in the perinuclear space. Depletion of this myosin not only affects endosome positioning, but also induces actin and lipid remodeling consistent with endosome maturation, including accumulation of F-actin and the endosomal lipid PI(3)P...
June 6, 2017: Cell Reports
https://www.readbyqxmd.com/read/28585210/adiponectin-resistance-in-obesity
#17
REVIEW
Atilla Engin
The decrease in adiponectin levels are negatively correlated with chronic subclinical inflammation markers in obesity. The hypertrophic adipocytes cause obesity-linked insulin resistance and metabolic syndrome. Furthermore, macrophage polarization is a key determinant regulating adiponectin receptor (AdipoR1/R2) expression and differential adiponectin-mediated macrophage inflammatory responses in obese individuals. In addition to decrease in adiponectin concentrations, the decline in AdipoR1/R2 mRNA expression leads to a decrement in adiponectin binding to cell membrane, and this turns into attenuation in the adiponectin effects...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28472298/adiponectin-stimulates-lipid-metabolism-via-ampk-in-rabbit-blastocysts
#18
Maria Schindler, Mareike Pendzialek, Katarzyna Joanna Grybel, Tom Seeling, Jacqueline Gürke, Bernd Fischer, Anne Navarrete Santos
STUDY QUESTION: How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts? SUMMARY ANSWER: In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover. WHAT IS KNOWN ALREADY: Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available...
July 1, 2017: Human Reproduction
https://www.readbyqxmd.com/read/28415720/the-function-of-oxytocin-a-potential-biomarker-for-prostate-cancer-diagnosis-and-promoter-of-prostate-cancer
#19
Huan Xu, Shi Fu, Qi Chen, Meng Gu, Juan Zhou, Chong Liu, Yanbo Chen, Zhong Wang
PURPOSE: To measure the level of oxytocin in serum and prostate cancer (PCa) tissue and study its effect on the proliferation of PCa cells. RESULTS: Oxytocin level in serum was significantly increased in PCa patients compared with the no-carcinoma individuals. Additionally, the levels of oxytocin and its receptor were also elevated in the PCa tissue. However, no significant difference existed among the PCa of various Gleason grades. Western blot analysis confirmed the previous results and revealed an increased expression level of APPL1...
May 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28176455/adiponectin-promotes-human-jaw-bone-marrow-mesenchymal-stem-cell-chemotaxis-via-cxcl1-and-cxcl8
#20
Yinfei Pu, Mengke Wang, Yingying Hong, Yuwei Wu, Zhihui Tang
Adiponectin (APN) is known to promote the osteogenic differentiation of human jaw bone marrow mesenchymal stem cells (h-JBMMSCs). However, the underlying mechanism has not been fully elucidated. Previously, we showed that APN could promote h-JBMMSC osteogenesis via APPL1-p38 by up-regulating osteogenesis-related genes. Here, we aimed to determine whether APN could promote h-JBMMSC chemotaxis through CXCL1/CXCL8. The CCK-8, wound healing and transwell assays were used to evaluate the proliferation, migration and chemotaxis of h-JBMMSCs with or without APN treatment...
July 2017: Journal of Cellular and Molecular Medicine
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