Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis.

Autor: Sarkar S; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Deiter C; Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Aurora, CO, 80045, USA., Kyle JE; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Guney MA; Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Aurora, CO, 80045, USA., Sarbaugh D; Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Aurora, CO, 80045, USA., Yin R; Department of Chemistry, Purdue University, West Lafayette, IN, 47907-2084, USA., Li X; Department of Chemistry, Purdue University, West Lafayette, IN, 47907-2084, USA., Cui Y; Environmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.; NanoString Technologies, Seattle, WA, 98109, USA., Ramos-Rodriguez M; Endocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu Fabra, 08003, Barcelona, Spain., Nicora CD; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Syed F; Center for Diabetes and Metabolic Diseases and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Juan-Mateu J; ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), 1070, Brussels, Belgium.; Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08003, Barcelona, Spain., Muralidharan C; Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA., Pasquali L; Endocrine Regulatory Genomics, Department of Experimental & Health Sciences, University Pompeu Fabra, 08003, Barcelona, Spain., Evans-Molina C; Center for Diabetes and Metabolic Diseases and the Herman B Wells Center for Pediatric Research, Indiana University School of Medicine, Indianapolis, IN, 46202, USA., Eizirik DL; ULB Center for Diabetes Research, Université Libre de Bruxelles (ULB), 1070, Brussels, Belgium., Webb-Robertson BM; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA.; Department of Biostatistics and Informatics, University of Colorado Anschutz Medical Center, Aurora, CO, 80045, USA., Burnum-Johnson K; Environmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Orr G; Environmental and Molecular Sciences Laboratory, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Laskin J; Department of Chemistry, Purdue University, West Lafayette, IN, 47907-2084, USA., Metz TO; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Mirmira RG; Kovler Diabetes Center and Department of Medicine, The University of Chicago, Chicago, IL, 60637, USA., Sussel L; Barbara Davis Center for Diabetes, University of Colorado Anschutz Medical Center, Aurora, CO, 80045, USA., Ansong C; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA., Nakayasu ES; Biological Sciences Division, Pacific Northwest National Laboratory, Richland, WA, 99354, USA. ernesto.nakayasu@pnnl.gov.
Jazyk: angličtina
Zdroj: Cell communication and signaling : CCS [Cell Commun Signal] 2024 Feb 21; Vol. 22 (1), pp. 141. Date of Electronic Publication: 2024 Feb 21.
DOI: 10.1186/s12964-023-01437-1
Abstrakt: Background: Lipids are regulators of insulitis and β-cell death in type 1 diabetes development, but the underlying mechanisms are poorly understood. Here, we investigated how the islet lipid composition and downstream signaling regulate β-cell death.
Methods: We performed lipidomics using three models of insulitis: human islets and EndoC-βH1 β cells treated with the pro-inflammatory cytokines interlukine-1β and interferon-γ, and islets from pre-diabetic non-obese mice. We also performed mass spectrometry and fluorescence imaging to determine the localization of lipids and enzyme in islets. RNAi, apoptotic assay, and qPCR were performed to determine the role of a specific factor in lipid-mediated cytokine signaling.
Results: Across all three models, lipidomic analyses showed a consistent increase of lysophosphatidylcholine species and phosphatidylcholines with polyunsaturated fatty acids and a reduction of triacylglycerol species. Imaging assays showed that phosphatidylcholines with polyunsaturated fatty acids and their hydrolyzing enzyme phospholipase PLA2G6 are enriched in islets. In downstream signaling, omega-3 fatty acids reduce cytokine-induced β-cell death by improving the expression of ADP-ribosylhydrolase ARH3. The mechanism involves omega-3 fatty acid-mediated reduction of the histone methylation polycomb complex PRC2 component Suz12, upregulating the expression of Arh3, which in turn decreases cell apoptosis.
Conclusions: Our data provide insights into the change of lipidomics landscape in β cells during insulitis and identify a protective mechanism by omega-3 fatty acids. Video Abstract.
(© 2024. Battelle Memorial Institute.)
Databáze: MEDLINE
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