2010
DOI: 10.1074/jbc.m109.084293
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Abstract: Our recent studies indicate that endoplasmic reticulum (ER) stress causes INS-1 cell apoptosis by a Ca2؉ -independent phospholipase A 2 (iPLA 2 ␤)-mediated mechanism that promotes ceramide generation via sphingomyelin hydrolysis and subsequent activation of the intrinsic pathway. To elucidate the association between iPLA 2 ␤ and ER stress, we compared ␤-cell lines generated from wild type (WT) and Akita mice. The Akita mouse is a spontaneous model of ER stress that develops hyperglycemia/ diabetes due to ER st… Show more

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Cited by 59 publications
(87 citation statements)
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“…SL diet-induced ␤ cell apoptosis may be mediated in part by the activation of the arachidonic acid cascade. This hypothesis is supported by reports that SREBP-1c-induced calcium-independent phospholipase A 2 (iPLA2␤) plays a key role in spontaneous ER stress and apoptosis in ␤ cells (32,33). To clarify the precise mechanisms for SL diet-induced ␤ cell apoptosis, further study using inhibitors of cyclooxygenase or lipoxygenases and mice deficient in phospholipases A 2 will be required.…”
Section: Discussionmentioning
confidence: 69%
“…SL diet-induced ␤ cell apoptosis may be mediated in part by the activation of the arachidonic acid cascade. This hypothesis is supported by reports that SREBP-1c-induced calcium-independent phospholipase A 2 (iPLA2␤) plays a key role in spontaneous ER stress and apoptosis in ␤ cells (32,33). To clarify the precise mechanisms for SL diet-induced ␤ cell apoptosis, further study using inhibitors of cyclooxygenase or lipoxygenases and mice deficient in phospholipases A 2 will be required.…”
Section: Discussionmentioning
confidence: 69%
“…The iPLA 2 ␤ is a member of the phospholipase A 2 family of enzymes, which hydrolyze the sn-2 fatty acid from membrane phospho-lipids to release a free fatty acid and a lysolipid (16). In pancreatic islets, iPLA 2 ␤ is predominantly localized in ␤-cells (17)(18)(19), and our studies reveal that expression and activity of iPLA 2 ␤ are increased when ␤-cells undergo ER stress-induced apoptosis (12,17,18,20,21). Activation of iPLA 2 ␤ also induces neutral sphingomyelinase 2 (NSMase2), resulting in accumulation of pro-apoptotic ceramides (12,17,18,22).…”
mentioning
confidence: 98%
“…In pancreatic islets, iPLA 2 ␤ is predominantly localized in ␤-cells (17)(18)(19), and our studies reveal that expression and activity of iPLA 2 ␤ are increased when ␤-cells undergo ER stress-induced apoptosis (12,17,18,20,21). Activation of iPLA 2 ␤ also induces neutral sphingomyelinase 2 (NSMase2), resulting in accumulation of pro-apoptotic ceramides (12,17,18,22). Various strategies (selective inhibitors, siRNA, and genetic-modulation) indicate a role for iPLA 2 ␤ and subsequent NSMase2-derived ceramides in ER stress-induced ␤-cell apoptosis (12, 17, 18, 20 -23).…”
mentioning
confidence: 98%
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