Lactosylceramide Interacts with and Activates Cytosolic Phospholipase A2α

Nakamura, Hiroyuki; Moriyama, Yoichi; Makiyama, Tomohiko; Emori, Shunsuke; Yamashita, Hisahiro; Yamazaki, Risa; Murayama, Toshihiko

doi:10.1074/jbc.m113.491431

Cited by 30 publications

(37 citation statements)

References 31 publications

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“…Our laboratory has reported recently that TNF-ainduced AA release is abolished by RNA interference of cPLA 2 a or glucosylceramide synthase (14). TNF-a induces the translocation of cPLA 2 a to the perinuclear regions, which is inhibited by treatment with inhibitor of glucosylceramide synthase.…”

Section: The Role Of Sphingolipid Metabolism In the Inflammatory Respmentioning

confidence: 99%

“…LacCer stimulates PECAM-1 (platelet endothelial cell adhesion molecule-1) expression in the adhesion and diapedesis of monocytes/ lymphocytes, which is inhibited by treatment with inhibitors of Ca 2+ -independent PLA 2 or cPLA 2 a (13). Recently, our laboratory has reported that down-regulation of cPLA 2 a using RNA interference abolishes the ability of LacCer to induce AA release in cells, suggesting that cPLA 2 a is the key PLA 2 downstream of LacCer (14). Treatment of cells with LacCer induces the translocation of full-length cPLA 2 a from the cytosol to the Golgi apparatus.…”

Section: Role Of Lactosylceramide (Laccer) In the Activity Of Cpla 2 Amentioning

confidence: 99%

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The Role of Sphingolipids in Arachidonic Acid Metabolism

Nakamura

Murayama

2014

J Pharmacol Sci

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Abstract. The arachidonic acid (AA) cascade is regulated mainly by the actions of two ratelimiting enzymes, phospholipase A 2 (PLA 2 ) and inducible cyclooxygenase-2 (COX-2). PLA 2 acts to generate AA, which serves as the precursor substrate for COX-2 in the metabolic pathway leading to prostaglandin production. Amongst more than 30 members of the PLA 2 family, cytosolic PLA 2 a (cPLA 2 a, group IVA) plays a major role in releasing AA from cellular membranes. Sphingolipids are a novel class of bioactive lipids that play key roles in the regulation of several cellular processes including growth, differentiation, inflammatory responses, and apoptosis. Recent studies implicated a regulatory function of sphingolipids in prostaglandin production. Whereas ceramide-1-phosphate and lactosylceramide activate cPLA 2 a directly, sphingosine-1-phosphate induces COX-2 expression. Sphingomyelin has been shown to inhibit the activity of cPLA 2 a. In addition, several sphingolipid analogs including a therapeutic agent currently used clinically are also reported to be inhibitors of cPLA 2 a. This review explores the role of sphingolipids in the regulation of cPLA 2 a and COX-2.

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Section: The Role Of Sphingolipid Metabolism In the Inflammatory Respmentioning

confidence: 99%

Section: Role Of Lactosylceramide (Laccer) In the Activity Of Cpla 2 Amentioning

confidence: 99%

The Role of Sphingolipids in Arachidonic Acid Metabolism

Nakamura

Murayama

2014

J Pharmacol Sci

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“…1 ). Binding of cPLA 2 ␣ to the Golgi may, in part, involve interaction of the C2 domain with sphingolipids, including ceramide-1-P and lactosylceramide (93)(94)(95)(96). Translocation of cPLA 2 ␣ to membrane is necessary but not suffi cient for cPLA 2 ␣ to release arachidonic acid ( 92 ).…”

Section: Downloaded Frommentioning

confidence: 99%

Cytosolic phospholipase A2: physiological function and role in disease

Leslie

2015

Journal of Lipid Research

350

257

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“…For example, Cer produced by sphingosine kinase-1 is required for MDCK cell growth (29). LacCer induced ROS generation and activation of ERK1/2 in cardiomyocytes (30), Ras activation in human aortic smooth muscle cells (31), and PLA2a activation via direct binding (32). We speculate that various lipids and several signaling pathways are involved in the active K-Ras-induced phenotypes.…”

Section: Discussionmentioning

confidence: 99%

Comparative lipid analysis in the normal and cancerous organoids of MDCK cells

Yoshizaki¹,

Ogiso

Okazaki

et al. 2016

J Biochem

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Epithelial organs are made of a well-polarized monolayer of epithelial cells, and their morphology is maintained strictly for their proper functioning. The roles of lipids are not only to generate the membrane, but also to provide the specific domains for signal transduction, or to transmit signals as second messengers. By using a liquid chromatography-electrospray ionization mass spectrometry (LC-MS)/MS method, we here analyzed sphingolipids in MDCK cysts under various conditions. Our result showed that, compared to the threedimensional cyst, the two-dimensional MDCK sheet is relatively enriched in sphingolipids. During cystogenesis, the contents of sphingomyelin (SM) and lactocylceramide (LacCer)-but, none those of ceramide, hexocylceramide, or GM3-are altered depending on their acyl chains. While the total SM is decreased more efficiently by SMS-1 knockdown than by SMS-2 knockdown, depletion of SMS-2, but not SMS-1, inhibits cyst growth. Finally upon the switching on of activated K-Ras expression which induces luminal cell filling, ceramide and LacCer are increased. Our parallel examinations of the microarray data for mRNA of sphingolipid metabolic enzymes failed to fully explain the remodelling of the sphingolipids of MDCK cysts. However, these results should be useful to investigate the cell-type-and structure-specific lipid metabolism.

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Lactosylceramide Interacts with and Activates Cytosolic Phospholipase A2α

Cited by 30 publications

References 31 publications

The Role of Sphingolipids in Arachidonic Acid Metabolism

The Role of Sphingolipids in Arachidonic Acid Metabolism

Cytosolic phospholipase A2: physiological function and role in disease

Comparative lipid analysis in the normal and cancerous organoids of MDCK cells

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