Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA2β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes

Type 1 diabetes (T1D) development, in part, is due to ER stress-induced β-cell apoptosis. Activation of the Ca2+-independent phospholipase A2 beta (iPLA2β) leads to the generation of pro-inflammatory eicosanoids, which contribute t...

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Autores principales:	Tomader Ali, Xiaoyong Lei, Suzanne E. Barbour, Akio Koizumi, Charles E. Chalfant, Sasanka Ramanadham
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	phospholipase A<sub>2</sub> sphingolipids diabetes apoptosis Organic chemistry QD241-441
Acceso en línea:	https://doaj.org/article/e36a69fd56814486a980de5987a4cd9a
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spelling	oai:doaj.org-article:e36a69fd56814486a980de5987a4cd9a2021-11-11T18:23:21ZAlterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes10.3390/molecules262163611420-3049https://doaj.org/article/e36a69fd56814486a980de5987a4cd9a2021-10-01T00:00:00Zhttps://www.mdpi.com/1420-3049/26/21/6361https://doaj.org/toc/1420-3049Type 1 diabetes (T1D) development, in part, is due to ER stress-induced β-cell apoptosis. Activation of the Ca<sup>2+</sup>-independent phospholipase A<sub>2</sub> beta (iPLA<sub>2</sub>β) leads to the generation of pro-inflammatory eicosanoids, which contribute to β-cell death and T1D. ER stress induces iPLA<sub>2</sub>β-mediated generation of pro-apoptotic ceramides via neutral sphingomyelinase (NSMase). To gain a better understanding of the impact of iPLA<sub>2</sub>β on sphingolipids (SLs), we characterized their profile in β-cells undergoing ER stress. ESI/MS/MS analyses followed by ANOVA/Student’s <i>t</i>-test were used to assess differences in sphingolipids molecular species in Vector (V) control and iPLA<sub>2</sub>β-overexpressing (OE) INS-1 and Akita (AK, spontaneous model of ER stress) and WT-littermate (AK-WT) β-cells. As expected, iPLA<sub>2</sub>β induction was greater in the OE and AK cells in comparison with V and WT cells. We report here that ER stress led to elevations in pro-apoptotic and decreases in pro-survival sphingolipids and that the inactivation of iPLA<sub>2</sub>β restores the sphingolipid species toward those that promote cell survival. In view of our recent finding that the SL profile in macrophages—the initiators of autoimmune responses leading to T1D—is not significantly altered during T1D development, we posit that the iPLA<sub>2</sub>β-mediated shift in the β-cell sphingolipid profile is an important contributor to β-cell death associated with T1D.Tomader AliXiaoyong LeiSuzanne E. BarbourAkio KoizumiCharles E. ChalfantSasanka RamanadhamMDPI AGarticlephospholipase A<sub>2</sub>sphingolipidsdiabetesapoptosisOrganic chemistryQD241-441ENMolecules, Vol 26, Iss 6361, p 6361 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	phospholipase A<sub>2</sub> sphingolipids diabetes apoptosis Organic chemistry QD241-441
spellingShingle	phospholipase A<sub>2</sub> sphingolipids diabetes apoptosis Organic chemistry QD241-441 Tomader Ali Xiaoyong Lei Suzanne E. Barbour Akio Koizumi Charles E. Chalfant Sasanka Ramanadham Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
description	Type 1 diabetes (T1D) development, in part, is due to ER stress-induced β-cell apoptosis. Activation of the Ca<sup>2+</sup>-independent phospholipase A<sub>2</sub> beta (iPLA<sub>2</sub>β) leads to the generation of pro-inflammatory eicosanoids, which contribute to β-cell death and T1D. ER stress induces iPLA<sub>2</sub>β-mediated generation of pro-apoptotic ceramides via neutral sphingomyelinase (NSMase). To gain a better understanding of the impact of iPLA<sub>2</sub>β on sphingolipids (SLs), we characterized their profile in β-cells undergoing ER stress. ESI/MS/MS analyses followed by ANOVA/Student’s <i>t</i>-test were used to assess differences in sphingolipids molecular species in Vector (V) control and iPLA<sub>2</sub>β-overexpressing (OE) INS-1 and Akita (AK, spontaneous model of ER stress) and WT-littermate (AK-WT) β-cells. As expected, iPLA<sub>2</sub>β induction was greater in the OE and AK cells in comparison with V and WT cells. We report here that ER stress led to elevations in pro-apoptotic and decreases in pro-survival sphingolipids and that the inactivation of iPLA<sub>2</sub>β restores the sphingolipid species toward those that promote cell survival. In view of our recent finding that the SL profile in macrophages—the initiators of autoimmune responses leading to T1D—is not significantly altered during T1D development, we posit that the iPLA<sub>2</sub>β-mediated shift in the β-cell sphingolipid profile is an important contributor to β-cell death associated with T1D.
format	article
author	Tomader Ali Xiaoyong Lei Suzanne E. Barbour Akio Koizumi Charles E. Chalfant Sasanka Ramanadham
author_facet	Tomader Ali Xiaoyong Lei Suzanne E. Barbour Akio Koizumi Charles E. Chalfant Sasanka Ramanadham
author_sort	Tomader Ali
title	Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
title_short	Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
title_full	Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
title_fullStr	Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
title_full_unstemmed	Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes
title_sort	alterations in β-cell sphingolipid profile associated with er stress and ipla<sub>2</sub>β: another contributor to β-cell apoptosis in type 1 diabetes
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/e36a69fd56814486a980de5987a4cd9a
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Alterations in β-Cell Sphingolipid Profile Associated with ER Stress and iPLA<sub>2</sub>β: Another Contributor to β-Cell Apoptosis in Type 1 Diabetes

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