Endoplasmic reticulum stress and eIF2α phosphorylation: The Achilles heel of pancreatic β cells
Reads0
Chats0
TLDR
Pancreatic β cells are sensitive to excessive endoplasmic reticulum stress and dysregulated eIF2α phosphorylation, as indicated by transcriptome data, monogenic forms of diabetes and pharmacological studies, and should be taken into consideration when devising new therapeutic approaches for diabetes.Abstract:
Background
Pancreatic β cell dysfunction and death are central in the pathogenesis of most if not all forms of diabetes. Understanding the molecular mechanisms underlying β cell failure is important to develop β cell protective approaches.read more
Citations
More filters
Sex differences in the development of diabetes in mice with deleted Wolframin (Wfs1) gene-an animal model for Wolfram syndrome: O/5/FRI/03
TL;DR: Low plasma insulin concentration with an increased proinsulin/insulin ratio in Wfs1KO males indicates possible disturbances in converting proins insulin to insulin which in long-term may lead to insulin deficiency.
Journal ArticleDOI
Alterations of redox and iron metabolism accompany the development of HIV latency
Iart Luca Shytaj,Bojana Lucic,Mattia Forcato,Carlotta Penzo,James M. Billingsley,Vibor Laketa,Steven E. Bosinger,Steven E. Bosinger,Mia Stanic,Francesco Gregoretti,Louis Antonelli,Gennaro Oliva,Christian K. Frese,Aleksandra Trifunovic,Bruno Galy,Clarissa Eibl,Guido Silvestri,Guido Silvestri,Silvio Bicciato,Andrea Savarino,Marina Lusic +20 more
TL;DR: It is shown that cells survive retroviral replication, both in vitro and in vivo in SIVmac‐infected macaques, by upregulating antioxidant pathways and the intertwined iron import pathway and that PML protein is degraded via the ubiquitin–proteasome pathway in productively infected cells, before latency establishment and after reactivation.
Journal ArticleDOI
Loss of MANF Causes Childhood-Onset Syndromic Diabetes Due to Increased Endoplasmic Reticulum Stress.
Hossam Montaser,Kashyap A. Patel,Diego Balboa,Hazem Ibrahim,Väinö Lithovius,Anna Näätänen,Vikash Chandra,Korcan Demir,Sezer Acar,Tawfeg Ben-Omran,Tawfeg Ben-Omran,Tawfeg Ben-Omran,Kevin Colclough,Jonathan M. Locke,Matthew Wakeling,Maria Lindahl,Andrew T. Hattersley,Jonna Saarimäki-Vire,Timo Otonkoski +18 more
TL;DR: In this article, the role of mesencephalic astrocyte-derived neurotrophic factor (MANF) in human β-cell development and function was investigated and it was shown that lack of MANF in humans results in diabetes due to increased ER stress.
Journal ArticleDOI
Proteotoxic Stress and Cell Death in Cancer Cells
Claudio Brancolini,Luca Iuliano +1 more
TL;DR: Understanding the cell death pathways engaged by proteotoxic stress is instrumental to better hijack the proliferative fate of cancer cells.
Journal ArticleDOI
Intersection of the ATF6 and XBP1 ER stress pathways in mouse islet cells
TL;DR: It is suggested that the XBP1 and ATF6 pathways are simultaneously activated in islet cells in response to acute stress and that ATF6α is required for full activation of X BP1 targets, but XBP2 is not required for activation of ATF6 α targets.
References
More filters
Journal ArticleDOI
Induction of Pluripotent Stem Cells from Adult Human Fibroblasts by Defined Factors
Kazutoshi Takahashi,Koji Tanabe,Mari Ohnuki,Megumi Narita,Tomoko Ichisaka,Kiichiro Tomoda,Shinya Yamanaka +6 more
TL;DR: It is demonstrated that iPS cells can be generated from adult human fibroblasts with the same four factors: Oct3/4, Sox2, Klf4, and c-Myc.
Journal ArticleDOI
Embryonic Stem Cell Lines Derived from Human Blastocysts
James A. Thomson,Joseph Itskovitz-Eldor,Sander S. Shapiro,Michelle A. Waknitz,Swiergiel Jennifer J,Vivienne S. Marshall,Jeffrey M. Jones +6 more
TL;DR: Human blastocyst-derived, pluripotent cell lines are described that have normal karyotypes, express high levels of telomerase activity, and express cell surface markers that characterize primate embryonic stem cells but do not characterize other early lineages.
Journal ArticleDOI
A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity.
Martin Jinek,Krzysztof Chylinski,Krzysztof Chylinski,Ines Fonfara,Michael H. Hauer,Jennifer A. Doudna,Emmanuelle Charpentier +6 more
TL;DR: This study reveals a family of endonucleases that use dual-RNAs for site-specific DNA cleavage and highlights the potential to exploit the system for RNA-programmable genome editing.
Journal ArticleDOI
The Genotype-Tissue Expression (GTEx) project
John T. Lonsdale,Jeffrey Thomas,Mike Salvatore,Rebecca Phillips,Edmund Lo,Saboor Shad,Richard Hasz,Gary Walters,Fernando U. Garcia,Nancy Young,Barbara A. Foster,Mike Moser,Ellen Karasik,Bryan Gillard,Kimberley Ramsey,Susan L. Sullivan,Jason Bridge,Harold Magazine,John Syron,Johnelle Fleming,Laura A. Siminoff,Heather M. Traino,Maghboeba Mosavel,Laura Barker,Scott D. Jewell,Daniel C. Rohrer,Dan Maxim,Dana Filkins,Philip Harbach,Eddie Cortadillo,Bree Berghuis,Lisa Turner,Eric Hudson,Kristin Feenstra,Leslie H. Sobin,James A. Robb,Phillip Branton,Greg E. Korzeniewski,Charles Shive,David Tabor,Liqun Qi,Kevin Groch,Sreenath Nampally,Steve Buia,Angela Zimmerman,Anna M. Smith,Robin Burges,Karna Robinson,Kim Valentino,Deborah Bradbury,Mark Cosentino,Norma Diaz-Mayoral,Mary Kennedy,Theresa Engel,Penelope Williams,Kenyon Erickson,Kristin G. Ardlie,Wendy Winckler,Gad Getz,Gad Getz,David S. DeLuca,MacArthur Daniel MacArthur,MacArthur Daniel MacArthur,Manolis Kellis,Alexander Thomson,Taylor Young,Ellen Gelfand,Molly Donovan,Yan Meng,George B. Grant,Deborah C. Mash,Yvonne Marcus,Margaret J. Basile,Jun Liu,Jun Zhu,Zhidong Tu,Nancy J. Cox,Dan L. Nicolae,Eric R. Gamazon,Hae Kyung Im,Anuar Konkashbaev,Jonathan K. Pritchard,Jonathan K. Pritchard,Matthew Stevens,Timothée Flutre,Xiaoquan Wen,Emmanouil T. Dermitzakis,Tuuli Lappalainen,Roderic Guigó,Jean Monlong,Michael Sammeth,Daphne Koller,Alexis Battle,Sara Mostafavi,Mark I. McCarthy,Manual Rivas,Julian Maller,Ivan Rusyn,Andrew B. Nobel,Fred A. Wright,Andrey A. Shabalin,Mike Feolo,Nataliya Sharopova,Anne Sturcke,Justin Paschal,James M. Anderson,Elizabeth L. Wilder,Leslie Derr,Eric D. Green,Jeffery P. Struewing,Gary F. Temple,Simona Volpi,Joy T. Boyer,Elizabeth J. Thomson,Mark S. Guyer,Cathy Ng,Assya Abdallah,Deborah Colantuoni,Thomas R. Insel,Susan E. Koester,Roger Little,Patrick Bender,Thomas Lehner,Yin Yao,Carolyn C. Compton,Jimmie B. Vaught,Sherilyn Sawyer,Nicole C. Lockhart,Joanne P. Demchok,Helen F. Moore +129 more
TL;DR: The Genotype-Tissue Expression (GTEx) project is described, which will establish a resource database and associated tissue bank for the scientific community to study the relationship between genetic variation and gene expression in human tissues.
Journal ArticleDOI
Signal integration in the endoplasmic reticulum unfolded protein response
David Ron,Peter Walter +1 more
TL;DR: Together, at least three mechanistically distinct arms of the UPR regulate the expression of numerous genes that function within the secretory pathway but also affect broad aspects of cell fate and the metabolism of proteins, amino acids and lipids.