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Beta Cells AND FoxO

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https://www.readbyqxmd.com/read/27875990/inverse-relationship-between-alzheimer-s-disease-and-cancer-and-other-factors-contributing-to-alzheimer-s-disease-a-systematic-review
#1
Ovais Shafi
BACKGROUND: The AD etiology is yet not properly known. Interactions among environmental factors, multiple susceptibility genes and aging, contribute to AD. This study investigates the factors that play role in causing AD and how changes in cellular pathways contribute to AD. METHODS: PUBMED database, MEDLINE database and Google Scholar were searched with no date restrictions for published articles involving cellular pathways with roles in cancers, cell survival, growth, proliferation, development, aging, and also contributing to Alzheimer's disease...
November 22, 2016: BMC Neurology
https://www.readbyqxmd.com/read/27037754/sirtuins-and-the-estrogen-receptor-as-regulators-of-the-mammalian-mitochondrial-upr-in-cancer-and-aging
#2
D Germain
By being both the source of ATP and the mediator of apoptosis, the mitochondria are key regulators of cellular life and death. Not surprisingly alterations in the biology of the mitochondria have implications in a wide array of diseases including cancer and age-related diseases such as neurodegeneration. To protect the mitochondria against damage the mitochondrial unfolded protein response (UPR(mt)) orchestrates several pathways, including the protein quality controls, the antioxidant machinery, oxidative phosphorylation, mitophagy, and mitochondrial biogenesis...
2016: Advances in Cancer Research
https://www.readbyqxmd.com/read/26845710/cratoxylum-formosum-extract-protects-against-amyloid-beta-toxicity-in-a-caenorhabditis-elegans-model-of-alzheimer-s-disease
#3
Roongpetch Keowkase, Natthida Weerapreeyakul
Amyloid-β, one of the hallmarks of Alzheimer's disease, is toxic to neurons and causes cell death in the brain. Oxidative stress is known to play an important role in Alzheimer's disease, and there is strong evidence linking oxidative stress to amyloid-β. The herbal plant "Tiew kon" (Cratoxylum formosum ssp. pruniflorum) is an indigenous vegetable that is grown in Southeast Asia. Many reports suggested that the twig extract from C. formosum possesses an antioxidant property. The purpose of this study was to investigate the protective effect of the twig extract from C...
April 2016: Planta Medica
https://www.readbyqxmd.com/read/26248647/the-new-biology-of-diabetes
#4
REVIEW
Utpal B Pajvani, Domenico Accili
Until recently, type 2 diabetes was seen as a disease caused by an impaired ability of insulin to promote the uptake and utilisation of glucose. Work on forkhead box protein O (FOXO) transcription factors revealed new aspects of insulin action that have led us to articulate a liver- and beta cell-centric narrative of diabetes pathophysiology and treatment. FOXO integrate a surprisingly diverse subset of biological functions to promote metabolic flexibility. In the liver, they controls the glucokinase/glucose-6-phosphatase switch and bile acid pool composition, directing carbons to glucose or lipid utilisation, thus providing a unifying mechanism for the two abnormalities of the diabetic liver: excessive glucose production and increased lipid synthesis and secretion...
November 2015: Diabetologia
https://www.readbyqxmd.com/read/26219891/dual-pi3k-mtor-inhibitor-xl765-sar245409-shows-superior-effects-to-sole-pi3k-xl147-sar245408-or-mtor-rapamycin-inhibition-in-prostate-cancer-cell-models
#5
Giovanni Luca Gravina, Andrea Mancini, Luca Scarsella, Alessandro Colapietro, Ana Jitariuc, Flora Vitale, Francesco Marampon, Enrico Ricevuto, Claudio Festuccia
Deregulation of phosphatidylinositol-3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathway contributes to prostate cancer development and progression. Here, we compared the in vitro effects of the dual PI3K/mTOR inhibitor (XL765) with those observed with the sole PI3K (XL147) or mTOR (rapamycin) inhibition in 2 non-tumor prostate epithelial cell lines, 8 prostate cancer cell lines, and 11 prostate cancer cell derivatives. We demonstrated that the XL765 treatment showed superior and proliferative effects of XL147 or rapamycin...
January 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/26039994/human-ortholog-of-drosophila-melted-impedes-smad2-release-from-tgf-%C3%AE-receptor-i-to-inhibit-tgf-%C3%AE-signaling
#6
Premalatha Shathasivam, Alexandra Kollara, Maurice J Ringuette, Carl Virtanen, Jeffrey L Wrana, Theodore J Brown
Drosophila melted encodes a pleckstrin homology (PH) domain-containing protein that enables normal tissue growth, metabolism, and photoreceptor differentiation by modulating Forkhead box O (FOXO), target of rapamycin, and Hippo signaling pathways. Ventricular zone expressed PH domain-containing 1 (VEPH1) is the mammalian ortholog of melted, and although it exhibits tissue-restricted expression during mouse development and is potentially amplified in several human cancers, little is known of its function. Here we explore the impact of VEPH1 expression in ovarian cancer cells by gene-expression profiling...
June 9, 2015: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/26038536/wnt-%C3%AE-catenin-signaling-contributes-to-skeletal-myopathy-in-heart-failure-via-direct-interaction-with-forkhead-box-o
#7
Katsuki Okada, Atsuhiko T Naito, Tomoaki Higo, Akito Nakagawa, Masato Shibamoto, Taku Sakai, Akihito Hashimoto, Yuki Kuramoto, Tomokazu Sumida, Seitaro Nomura, Masamichi Ito, Toshihiro Yamaguchi, Toru Oka, Hiroshi Akazawa, Jong-Kook Lee, Sachio Morimoto, Yasushi Sakata, Ichiro Shiojima, Issei Komuro
BACKGROUND: There are changes in the skeletal muscle of patients with chronic heart failure (CHF), such as volume reduction and fiber type shift toward fatigable type IIb fiber. Forkhead box O (FoxO) signaling plays a critical role in the development of skeletal myopathy in CHF, and functional interaction between FoxO and the Wnt signal mediator β-catenin was previously demonstrated. We have recently reported that serum of CHF model mice activates Wnt signaling more potently than serum of control mice and that complement C1q mediates this activation...
July 2015: Circulation. Heart Failure
https://www.readbyqxmd.com/read/26025205/the-critical-role-of-akt-in-cardiovascular-function
#8
REVIEW
Prasanna Abeyrathna, Yunchao Su
Akt kinase, a member of AGC kinases, is important in many cellular functions including proliferation, migration, cell growth and metabolism. There are three known Akt isoforms which play critical and diverse roles in the cardiovascular system. Akt activity is regulated by its upstream regulatory pathways at transcriptional and post-translational levels. Beta-catenin/Tcf-4, GLI1 and Stat-3 are some of few known transcriptional regulators of AKT gene. Threonine 308 and serine 473 are the two critical phosphorylation sites of Akt1...
November 2015: Vascular Pharmacology
https://www.readbyqxmd.com/read/25806826/the-pax3-foxo1-fusion-protein-present-in-rhabdomyosarcoma-interferes-with-normal-foxo-activity-and-the-tgf-%C3%AE-pathway
#9
Michel Schmitt-Ney, Giovanni Camussi
PAX3-FOXO1 (PAX3-FKHR) is the fusion protein produced by the genomic translocation that characterizes the alveolar subtype of Rhabdomyosarcoma, a pediatric sarcoma with myogenic phenotype. PAX3-FOXO1 is an aberrant but functional transcription factor. It retains PAX3-DNA-binding activity and functionally overlaps PAX3 function while also disturbing it, in particular its role in myogenic differentiation. We herein show that PAX3-FOXO1 interferes with normal FOXO function. PAX3-FOXO1 affects FOXO-family member trans-activation capability and the FOXO-dependent TGF-β response...
2015: PloS One
https://www.readbyqxmd.com/read/25740230/aplp1-promotes-dfoxo-dependent-cell-death-in-drosophila
#10
Xingjun Wang, Yeqing Ma, Yu Zhao, Yujun Chen, Yujia Hu, Changyan Chen, Yingyao Shao, Lei Xue
The amyloid precursor like protein-1 (APLP1) belongs to the amyloid precursor protein family that also includes the amyloid precursor protein (APP) and the amyloid precursor like protein-2 (APLP2). Though the three proteins share similar structures and undergo the same cleavage processing by α-, β- and γ-secretases, APLP1 shows divergent subcellular localization from that of APP and APLP2, and thus, may perform distinct roles in vivo. While extensive studies have been focused on APP, which is implicated in the pathogenesis of Alzheimer's disease, the functions of APLP1 remain largely elusive...
June 2015: Apoptosis: An International Journal on Programmed Cell Death
https://www.readbyqxmd.com/read/25670795/akt1-signaling-coordinates-bmp-signaling-and-%C3%AE-catenin-activity-to-regulate-second-heart-field-progenitor-development
#11
Wen Luo, Xia Zhao, Hengwei Jin, Lichan Tao, Jingai Zhu, Huijuan Wang, Brian A Hemmings, Zhongzhou Yang
Second heart field (SHF) progenitors exhibit continued proliferation and delayed differentiation, which are modulated by FGF4/8/10, BMP and canonical Wnt/β-catenin signaling. PTEN-Akt signaling regulates the stem cell/progenitor cell homeostasis in several systems, such as hematopoietic stem cells, intestinal stem cells and neural progenitor cells. To address whether PTEN-Akt signaling is involved in regulating cardiac progenitors, we deleted Pten in SHF progenitors. Deletion of Pten caused SHF expansion and increased the size of the SHF derivatives, the right ventricle and the outflow tract...
February 15, 2015: Development
https://www.readbyqxmd.com/read/25578861/foxo3a-modulates-wnt-%C3%AE-catenin-signaling-and-suppresses-epithelial-to-mesenchymal-transition-in-prostate-cancer-cells
#12
Hao Liu, Jiang Yin, Hongsheng Wang, Guanmin Jiang, Min Deng, Ge Zhang, Xianzhang Bu, Shaohui Cai, Jun Du, Zhimin He
Emerging evidence has revealed a negative correlation between Forkhead box-O (FOXO) expression and prostate cancer grade and spread, indicating its role as a suppressor of prostate cancer metastasis. However, there is still incomplete understanding about the role of FOXO transcription factors in prostate cancer progression. In this investigation, we demonstrate that FOXO3a significantly inhibits the expression β-catenin in prostate cancer cells. The mechanism of inhibiting β-catenin expression involves the FOXO3a-mediated transactivated microRNA-34b/c, which consequently suppressed β-catenin mRNA expression by targeting the untranslated regions (UTRs) of β-catenin...
March 2015: Cellular Signalling
https://www.readbyqxmd.com/read/25503443/threonine-32-thr32-of-foxo3-is-critical-for-tgf-%C3%AE-induced-apoptosis-via-bim-in-hepatocarcinoma-cells
#13
Xiangxuan Zhao, Yong Liu, Lei Du, Leya He, Biyun Ni, Junbo Hu, Dahai Zhu, Quan Chen
Transforming growth factor-β (TGF-β) exerts apoptotic effects on various types of malignant cells, including liver cancer cells. However, the precise mechanisms by which TGF-β induces apoptosis remain poorly known. In the present study, we have showed that threonine 32 (Thr32) residue of FoxO3 is critical for TGF-β to induce apoptosis via Bim in hepatocarcinoma Hep3B cells. Our data demonstrated that TGF-β induced FoxO3 activation through specific de-phosphorylation at Thr32. TGF-β-activated FoxO3 cooperated with Smad2/3 to mediate Bim up-regulation and apoptosis...
February 2015: Protein & Cell
https://www.readbyqxmd.com/read/25448064/nephrin-a-transmembrane-protein-is-involved-in-pancreatic-beta-cell-survival-signaling
#14
Katerina Kapodistria, Effie-Photini Tsilibary, Panagiotis Politis, Petros Moustardas, Aristidis Charonis, Paraskevi Kitsiou
Nephrin, a cell surface signaling receptor, regulates podocyte function in health and disease. We study the role of nephrin in β-cell survival signaling. We report that in mouse islet β-cells and the mouse pancreatic beta-cell line (βTC-6 cells) nephrin is associated and partly co-localized with PI3-kinase. Incubation of cells with functional anti-nephrin antibodies induced nephrin clustering at the plasma membrane, nephrin phosphorylation and recruitment of PI3-kinase to nephrin thus resulting in increased PI3K-dependent Akt phosphorylation and augmented phosphorylation/inhibition of pro-apoptotic Bad and FoxO...
January 15, 2015: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/25261981/c10orf10-depp-a-transcriptional-target-of-foxo3-regulates-ros-sensitivity-in-human-neuroblastoma
#15
Stefan Salcher, Judith Hagenbuchner, Kathrin Geiger, Maximilian A Seiter, Johannes Rainer, Reinhard Kofler, Martin Hermann, Ursula Kiechl-Kohlendorfer, Michael J Ausserlechner, Petra Obexer
BACKGROUND: FOXO transcription factors control cellular levels of reactive oxygen species (ROS) which critically contribute to cell survival and cell death in neuroblastoma. In the present study we investigated the regulation of C10orf10/DEPP by the transcription factor FOXO3. As a physiological function of C10orf10/DEPP has not been described so far we analyzed its effects on cellular ROS detoxification and death sensitization in human neuroblastoma cells. METHODS: The effect of DEPP on cellular ROS was measured by catalase activity assay and live cell fluorescence microscopy using the ROS-sensitive dye reduced MitoTracker Red CM-H2XROS...
September 28, 2014: Molecular Cancer
https://www.readbyqxmd.com/read/25069953/evolutionary-acquisition-of-cysteines-determines-foxo-paralog-specific-redox-signaling
#16
Marrit Putker, Harmjan R Vos, Kim van Dorenmalen, Hesther de Ruiter, Ana G Duran, Berend Snel, Boudewijn M T Burgering, Michiel Vermeulen, Tobias B Dansen
UNLABELLED: Reduction-oxidation (redox) signaling, the translation of an oxidative intracellular environment into a cellular response, is mediated by the reversible oxidation of specific cysteine thiols. The latter can result in disulfide formation between protein hetero- or homodimers that alter protein function until the local cellular redox environment has returned to the basal state. We have previously shown that this mechanism promotes the nuclear localization and activity of the Forkhead Box O4 (FOXO4) transcription factor...
January 1, 2015: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/25002589/sirtuin1-sirt1-promotes-cortical-bone-formation-by-preventing-%C3%AE-catenin-sequestration-by-foxo-transcription-factors-in-osteoblast-progenitors
#17
Srividhya Iyer, Li Han, Shoshana M Bartell, Ha-Neui Kim, Igor Gubrij, Rafael de Cabo, Charles A O'Brien, Stavros C Manolagas, Maria Almeida
A decline of the levels and activity of Sirtuin1 (Sirt1), a NAD(+) class III histone deacetylase, with age contributes to the development of several diseases including type 2 diabetes, neurodegeneration, inflammation, and cancer. The anti-aging effects of Sirt1 evidently result from the deacetylation of many transcription factors and co-factors including members of the Forkhead box O (FoxO) family and β-catenin. Wnt/β-catenin is indispensable for osteoblast generation. FoxOs, on the other hand, sequester β-catenin and inhibit osteoprogenitor proliferation...
August 29, 2014: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/24832605/foxo-mediates-app-induced-aicd-dependent-cell-death
#18
X Wang, Z Wang, Y Chen, X Huang, Y Hu, R Zhang, M S Ho, L Xue
The amyloid precursor protein (APP) is a broadly expressed transmembrane protein that has a significant role in the pathogenesis of Alzheimer's disease (AD). APP can be cleaved at multiple sites to generate a series of fragments including the amyloid β (Aβ) peptides and APP intracellular domain (AICD). Although Aβ peptides have been proposed to be the main cause of AD pathogenesis, the role of AICD has been underappreciated. Here we report that APP induces AICD-dependent cell death in Drosophila neuronal and non-neuronal tissues...
May 15, 2014: Cell Death & Disease
https://www.readbyqxmd.com/read/24747665/foxo3-and-related-transcription-factors-in-development-aging-and-exceptional-longevity
#19
Arnold J Kahn
In June 2013, a workshop was convened in San Francisco to explore, in depth, the role of the Forkhead transcription factor FOXO3 (and related FOXOs) in development, aging, and, in particular, exceptional longevity. The presentations covered results derived from model systems, computational analysis and bioinformatics, and genomics and genome-wide association studies of a number of cohorts. Although the data collectively strongly reinforce FOXO3 and the FOXO/FOXO3 pathway as very important determinants in aging and life span, much of the detail of how the latter is achieved still remains unknown, in part, because of the very large number of genes (~2,200 in Caenorhabditis elegans) the transcription factor is involved in helping regulate...
April 2015: Journals of Gerontology. Series A, Biological Sciences and Medical Sciences
https://www.readbyqxmd.com/read/24437485/foxo1-is-a-negative-regulator-of-fsh%C3%AE-gene-expression-in-basal-and-gnrh-stimulated-conditions-in-female
#20
Young-Suk Choi, Hyeon Jeong Lee, Cheol Ryong Ku, Yoon Hee Cho, Mi Ran Seo, Yoo Jeoung Lee, Eun Jig Lee
The importance of forkhead box class O (FoxO) proteins in reproductive endocrinology has been confirmed by age-dependent infertility in females in a FoxO3a-knockout mouse model. In this study, FoxO1 was detected in gonadotropes in the anterior pituitary. Overexpression of FoxO1 in primary pituitary cells decreased FSHβ gene expression in both basal and GnRH-stimulated conditions, and this result was replicated by the human FSHβ promoter activity. Although direct binding of FoxO1 to FoxO-binding element (FBE) (at -124 to -119 bp of the human FSHβ promoter) was not detected in an electrophoretic mobility shift assay, a DNA pull-down assay and transfection study using the mutant FBE reporter vector revealed that FBE is necessary in FSHβ suppression by FoxO1, suggestive of other cofactor requirements...
June 2014: Endocrinology
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