Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment

Details

Serval ID
serval:BIB_07427F5B73A3
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Proteasomal degradation of the histone acetyl transferase p300 contributes to beta-cell injury in a diabetes environment
Journal
Cell Death Dis
Author(s)
Ruiz L., Gurlo T., Ravier M. A., Wojtusciszyn A., Mathieu J., Brown M. R., Broca C., Bertrand G., Butler P. C., Matveyenko A. V., Dalle S., Costes S.
ISSN
2041-4889 (Electronic)
Publication state
Published
Issued date
2018
Volume
9
Number
6
Pages
600
Language
english
Notes
Ruiz, Lucie
Gurlo, Tatyana
Ravier, Magalie A
Wojtusciszyn, Anne
Mathieu, Julia
Brown, Matthew R
Broca, Christophe
Bertrand, Gyslaine
Butler, Peter C
Matveyenko, Aleksey V
Dalle, Stephane
Costes, Safia
eng
R01 DK059579/DK/NIDDK NIH HHS/
Research Support, Non-U.S. Gov't
England
Cell Death Dis. 2018 May 22;9(6):600. doi: 10.1038/s41419-018-0603-0.
Abstract
In type 2 diabetes, amyloid oligomers, chronic hyperglycemia, lipotoxicity, and pro-inflammatory cytokines are detrimental to beta-cells, causing apoptosis and impaired insulin secretion. The histone acetyl transferase p300, involved in remodeling of chromatin structure by epigenetic mechanisms, is a key ubiquitous activator of the transcriptional machinery. In this study, we report that loss of p300 acetyl transferase activity and expression leads to beta-cell apoptosis, and most importantly, that stress situations known to be associated with diabetes alter p300 levels and functional integrity. We found that proteasomal degradation is the mechanism subserving p300 loss in beta-cells exposed to hyperglycemia or pro-inflammatory cytokines. We also report that melatonin, a hormone produced in the pineal gland and known to play key roles in beta-cell health, preserves p300 levels altered by these toxic conditions. Collectively, these data imply an important role for p300 in the pathophysiology of diabetes.
Keywords
Acetylation, Animals, Apoptosis/drug effects, Cytokines/metabolism, Diabetes Mellitus/*enzymology/*pathology, E1A-Associated p300 Protein/genetics/*metabolism, Glucose/toxicity, Histones/metabolism, Humans, Inflammation Mediators/metabolism, Insulin-Secreting Cells/drug effects/*enzymology/*pathology, Male, Melatonin/metabolism, Mice, Inbred C57BL, Proteasome Endopeptidase Complex/*metabolism, *Proteolysis/drug effects, RNA, Messenger/genetics/metabolism, Receptors, Melatonin/metabolism, Signal Transduction
Pubmed
Create date
14/06/2021 9:59
Last modification date
18/09/2021 6:38
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