دورية أكاديمية
Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis
| العنوان: | Regulation of β-cell death by ADP-ribosylhydrolase ARH3 via lipid signaling in insulitis |
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| المؤلفون: | Soumyadeep Sarkar, Cailin Deiter, Jennifer E. Kyle, Michelle A. Guney, Dylan Sarbaugh, Ruichuan Yin, Xiangtang Li, Yi Cui, Mireia Ramos-Rodriguez, Carrie D. Nicora, Farooq Syed, Jonas Juan-Mateu, Charanya Muralidharan, Lorenzo Pasquali, Carmella Evans-Molina, Decio L. Eizirik, Bobbie-Jo M. Webb-Robertson, Kristin Burnum-Johnson, Galya Orr, Julia Laskin, Thomas O. Metz, Raghavendra G. Mirmira, Lori Sussel, Charles Ansong, Ernesto S. Nakayasu |
| المصدر: | Cell Communication and Signaling, Vol 22, Iss 1, Pp 1-17 (2024) |
| بيانات النشر: | BMC, 2024. |
| سنة النشر: | 2024 |
| المجموعة: | LCC:Medicine LCC:Cytology |
| مصطلحات موضوعية: | Medicine, Cytology, QH573-671 |
| الوصف: | Abstract 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 |
| نوع الوثيقة: | article |
| وصف الملف: | electronic resource |
| اللغة: | English |
| تدمد: | 1478-811X |
| العلاقة: | https://doaj.org/toc/1478-811XTest |
| DOI: | 10.1186/s12964-023-01437-1 |
| الوصول الحر: | https://doaj.org/article/6b57b4f4064a4390ae8f0840effa40acTest |
| رقم الانضمام: | edsdoj.6b57b4f4064a4390ae8f0840effa40ac |
| قاعدة البيانات: | Directory of Open Access Journals |
Full Text Finder | تدمد: | 1478811X |
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| DOI: | 10.1186/s12964-023-01437-1 |