scholarly journals Critical role for classical PKC in activating Akt by phospholipase A2-modified LDL in monocytic cells

2007 ◽  
Vol 73 (4) ◽  
pp. 833-840 ◽  
Author(s):  
Stefan Preiß ◽  
Dmitry Namgaladze ◽  
Bernhard Brüne
Keyword(s):  
Phospholipase A2 ◽  
Critical Role ◽  
Monocytic Cells ◽  
Modified Ldl

Monocytic cells derived from human embryonic stem cells and fetal liver share common differentiation pathways and homeostatic functions

Blood ◽  
2011 ◽  
Vol 117 (11) ◽  
pp. 3065-3075 ◽  
Author(s):  
Olena Klimchenko ◽  
Antonio Di Stefano ◽  
Birgit Geoerger ◽  
Sofiane Hamidi ◽  
Paule Opolon ◽  
...  
Keyword(s):  
Stem Cells ◽  
Embryonic Stem Cells ◽  
Human Embryonic Stem Cells ◽  
Fetal Liver ◽  
Critical Role ◽  
Embryonic Stem ◽  
Blood Monocytes ◽  
Monocytic Cell ◽  
Monocytic Cells

Abstract The early emergence of macrophages and their large pattern of tissue distribution during development suggest that they may play a critical role in the initial steps of embryogenesis. In the present study, we show that monocytic cells derived from human embryonic stem cells (hESCs) and from fetal liver follow a differentiation pathway different to that of adult cells, leading to specific functions. Embryonic and fetal monocytic cells differentiated from a CD14lowCD16− precursor to form CD14highCD16+ cells without producing the CD14highCD16− cell population that predominates in adult peripheral blood. Both demonstrated an enhanced expression of genes encoding tissue-degrading enzymes, chemokines, and scavenger receptors, as was previously reported for M2 macrophages. Compared with adult blood monocytes, embryonic and fetal monocytic cells secreted high amounts of proteins acting on tissue remodeling and angiogenesis, and most of them expressed the Tie2 receptor. Furthermore, they promoted vascular remodeling in xenotransplanted human tumors. These findings suggest that the regulation of human fetal and embryonic monocytic cell differentiation leads to the generation of cells endowed mainly with anti-inflammatory and remodeling functions. Trophic and immunosuppressive functions of M2-polarized macrophages link fetus and tumor development, and hESCs offer a valuable experimental model for in vitro studies of mechanisms sustaining these processes.

scholarly journals Critical Role of TLR2 and MyD88 for Functional Response of Macrophages to a Group IIA-Secreted Phospholipase A2 from Snake Venom

PLoS ONE ◽  
2014 ◽  
Vol 9 (4) ◽  
pp. e93741 ◽  
Author(s):  
Elbio Leiguez ◽  
Karina Cristina Giannotti ◽  
Vanessa Moreira ◽  
Márcio Hideki Matsubara ◽  
José María Gutiérrez ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Functional Response ◽  
Snake Venom ◽  
Critical Role ◽  
Secreted Phospholipase A2

scholarly journals A GPI processing phospholipase A2, PGAP6, modulates Nodal signaling in embryos by shedding CRIPTO

2016 ◽  
Vol 215 (5) ◽  
pp. 705-718 ◽  
Author(s):  
Gun-Hee Lee ◽  
Morihisa Fujita ◽  
Katsuyoshi Takaoka ◽  
Yoshiko Murakami ◽  
Yoshitaka Fujihara ◽  
...  
Keyword(s):  
Cell Membrane ◽  
Embryonic Development ◽  
Phospholipase A2 ◽  
Phospholipase D ◽  
Critical Role ◽  
Early Embryonic Development ◽  
Nodal Signaling ◽  
Common Features ◽  
Highly Sensitive ◽  
Anterior Posterior

Glycosylphosphatidylinositol-anchored proteins (GPI-APs) can be shed from the cell membrane by GPI cleavage. In this study, we report a novel GPI-processing enzyme, termed post-glycosylphosphatidylinositol attachment to proteins 6 (PGAP6), which is a GPI-specific phospholipase A2 mainly localized at the cell surface. CRIPTO, a GPI-AP, which plays critical roles in early embryonic development by acting as a Nodal coreceptor, is a highly sensitive substrate of PGAP6, whereas CRYPTIC, a close homologue of CRIPTO, is not sensitive. CRIPTO processed by PGAP6 was released as a lysophosphatidylinositol-bearing form, which is further cleaved by phospholipase D. CRIPTO shed by PGAP6 was active as a coreceptor in Nodal signaling, whereas cell-associated CRIPTO activity was reduced when PGAP6 was expressed. Homozygous Pgap6 knockout mice showed defects in early embryonic development, particularly in the formation of the anterior–posterior axis, which are common features with Cripto knockout embryos. These results suggest PGAP6 plays a critical role in Nodal signaling modulation through CRIPTO shedding.

scholarly journals MD2 blockade prevents modified LDL-induced retinal injury in diabetes by suppressing NADPH oxidase-4 interaction with Toll-like receptor-4

2021 ◽  
Author(s):  
Huaicheng Chen ◽  
Tao Yan ◽  
Zongming Song ◽  
Shilong Ying ◽  
Beibei Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Nadph Oxidase ◽  
Cell Injury ◽  
Critical Role ◽  
Inflammatory Factor ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Modified Ldl ◽  
Nadph Oxidase 4 ◽  
Retinal Injury

AbstractModified LDL-induced inflammation and oxidative stress are involved in the pathogenesis of diabetic retinopathy. Recent studies have also shown that modified LDL activates Toll-like receptor 4 (TLR4) to mediate retinal injury. However, the mechanism by which modified LDL activates TLR4 and the potential role of the TLR4 coreceptor myeloid differentiation protein 2 (MD2) are not known. In this study, we inhibited MD2 with the chalcone derivatives L2H17 and L6H21 and showed that MD2 blockade protected retinal Müller cells against highly oxidized glycated-LDL (HOG-LDL)-induced oxidative stress, inflammation, and apoptosis. MD2 inhibition reduced oxidative stress by suppressing NADPH oxidase-4 (NOX4). Importantly, HOG-LDL activated TLR4 and increased the interaction between NOX4 and TLR4. MD2 was required for the activation of these pathways, as inhibiting MD2 prevented the association of NOX4 with TLR4 and reduced NOX4-mediated reactive oxygen species production and TLR4-mediated inflammatory factor production. Furthermore, treatment of diabetic mice with L2H17 significantly reduced LDL extravasation in the retina and prevented retinal dysfunction and apoptosis by suppressing the TLR4/MD2 pathway. Our findings provide evidence that MD2 plays a critical role in mediating modified LDL-induced cell injury in the retina and suggest that targeting MD2 may be a potential therapeutic strategy.

Phospholipase A2-modified LDL particles retain the generated hydrolytic products and are more atherogenic at acidic pH

2009 ◽  
Vol 207 (2) ◽  
pp. 352-359 ◽  
Author(s):  
Katariina Lähdesmäki ◽  
Riia Plihtari ◽  
Pasi Soininen ◽  
Eva Hurt-Camejo ◽  
Mika Ala-Korpela ◽  
...  
Keyword(s):  
Phospholipase A2 ◽  
Acidic Ph ◽  
Modified Ldl ◽  
Ldl Particles

scholarly journals Nuclear signalling by Rac GTPase: essential role of phospholipase A2

1997 ◽  
Vol 326 (2) ◽  
pp. 333-337 ◽  
Author(s):  
Byung-Chul KIM ◽  
Jae-Hong KIM
Keyword(s):  
Phospholipase A2 ◽  
Critical Role ◽  
Specific Inhibitor ◽  
Major Product ◽  
Luciferase Reporter ◽  
Dependent Manner ◽  
Luciferase Reporter Gene ◽  
Inhibitory Protein ◽  
Rac Gtpase

Rac, one member of Rho family GTPases, stimulates c-fos serum response element (SRE)–luciferase reporter gene in Rat-2 fibroblast cells. By transient transfection analysis, we demonstrated that the activation of phospholipase A2 (PLA2) and the subsequent production of arachidonic acid (AA) are essential for Rac-induced c-fos SRE activation, implying a critical role for PLA2 in the Rac-signalling pathway to the nucleus. Either pretreatment with mepacrine, a specific inhibitor of PLA2, or co-transfection with the expression plasmid of lipocortin-1, a proposed inhibitory protein of PLA2, selectively abolished RacV12-induced SRE activation. Further, we demonstrated that subsequent metabolism of AA, a major product of Rac-activated PLA2, by lipoxygenase (LO) is essential for Rac-induced c-fos SRE activation. In agreement with the role of the PLA2–AA–LO cascade as a potential mediator of Rac signalling to the nucleus, the addition of exogenous AA stimulated c-fos SRE-luciferase activity in an LO-dependent manner. Together, our results demonstrate that ‘Rac-activated PLA2 and subsequent AA metabolism by LO’ constitute a novel and specific pathway in Rac GTPase-induced c-fos SRE activation.

scholarly journals Organochlorine Insecticides Induce NADPH Oxidase-Dependent Reactive Oxygen Species in Human Monocytic Cells via Phospholipase A2/Arachidonic Acid

2015 ◽  
Vol 28 (4) ◽  
pp. 570-584 ◽  
Author(s):  
Lee C. Mangum ◽  
Abdolsamad Borazjani ◽  
John V. Stokes ◽  
Anberitha T. Matthews ◽  
Jung Hwa Lee ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Arachidonic Acid ◽  
Nadph Oxidase ◽  
Phospholipase A2 ◽  
Reactive Oxygen ◽  
Oxygen Species ◽  
Monocytic Cells ◽  
Organochlorine Insecticides
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