Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase/PKB, JNK and ERK1/2 pathways

Gangoiti, Patricia; Granado, María H.; Wang, Shih‐Wei; Kong, Jennifer Y.; Steinbrecher, Urs P.; Gómez-Muñoz, Antonio

doi:10.1016/j.cellsig.2007.12.008

Cited by 126 publications

(127 citation statements)

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“…This effect was recently also observed in BMDM (Gangoiti et al, 2008b). Specifically, we found that C1P increased DNA synthesis and cell number in macrophages that were pre-incubated with low concentrations of M-CSF to maintain a steadystate cell culture (equal cell growth and death).…”

Section: C1p Regulates Cell Growth and Deathsupporting

confidence: 80%

“…Both C1P-stimulated PKB phosphorylation and the pro-survival effect of C1P were blocked by the PI-3K inhibitors wortmannin and LY294002. Another relevant finding was that C1P caused IB phosphorylation, stimulation of the DNA binding activity of NF-B and up-regulation of the expression of anti-apoptotic Bcl-X L in macrophages (Gangoiti et al, 2008b;Gomez-Munoz et al, 2005). These findings suggest that stimulation of the PI-3K/PKB/ NF-B pathway, together with the inhibition of acid SMase, and with SPT inhibition, play crucial roles in the anti-apoptotic effect of C1P in macrophages.…”

Section: C1p Regulates Cell Growth and Deathmentioning

confidence: 90%

“…This treatment inhibited AA release and PGE 2 production in response to a calcium ionophore and to interleukin 1 (IL-1 (Chalfant and Spiegel, 2005;Pettus et al, 2003). Of relevance, C1P was shown to be generated by the actions of either a calcium ionophore or IL-1 on A549 lung adenocarcinoma cells (Pettus et al, 2003), and M-CSF on bone A c c e p t e d M a n u s c r i p t 4 marrow-derived macrophages (BMDM) (Gangoiti et al, 2008b). A crucial discovery was the direct implication of C1P in the inflammatory response.…”

Section: C1p Regulates Inflammationmentioning

confidence: 99%

“…Specifically, we found that C1P increased DNA synthesis and cell number in macrophages that were pre-incubated with low concentrations of M-CSF to maintain a steadystate cell culture (equal cell growth and death). Like for most growth factors, C1P stimulated cell proliferation through activation of well-established mitogenic pathways including mitogenactivated protein kinase kinase (MEK)/Extracellular regulated kinases 1/2 (ERK1/2), phosphatidylinositol 3-kinase (PI-3K)/protein kinase B (PKB, also known as Akt), and c-Jun terminal kinase (JNK) (Gangoiti et al, 2008b). Additionally, C1P increased expression of a major target of the PI-3K/PKB pathway, glycogen synthase kinase-3β (GSK-3β).…”

Section: C1p Regulates Cell Growth and Deathmentioning

confidence: 99%

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Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Levi

Meijler

Gómez-Muñoz

et al. 2010

Molecular and Cellular Endocrinology

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. Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1). Molecular and Cellular Endocrinology, Elsevier, 2009, 314 (2) This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Page 1 Ceramide-1-phosphate (C1P) is known as a second messenger regulating a multitude of processes including cell growth, apoptosis and inflammation. Exciting recent findings now suggest that C1P can stimulate macrophages migration in an extra-cellular manner via a G protein-coupled receptor (GPCR). Interestingly, a synthetic C1P analog, named phospho-ceramide analogue-1 (PCERA-1), was recently described as a potent in-vivo anti-inflammatory agent, and was suggested to act on macrophages in an extra-cellular manner via a GPCR. Here we summarize and compare the receptor-mediated as well as receptor-independent activities of natural C1P and its synthetic analog. We also provide experimental data in support of distinct C1P and PCERA-1 receptors.Page 3 of 20A c c e p t e d M a n u s c r i p t 3 IntroductionIt is well-established that sphingolipids are crucial metabolites for controlling cell and tissue homeostasis. In particular, ceramides induce cell cycle arrest and are potent inducers of apoptosis. Also, ceramides play crucial roles in the regulation of cell differentiation, and inflammation (Hannun et al., 1986;Hannun, 1994;Hannun and Obeid, 1995;Hannun, 1996;Hannun and Obeid, 2002;Kolesnick, 1994;Kolesnick, 1987;Kolesnick and Hemer, 1990;Kolesnick et al., 2000;Merrill and Jones, 1990;Merrill et al., 1997;Merrill, 2002;Spiegel and Merrill, 1996).Ceramides are generated either by de novo synthesis, or by the action of different sphingomyelinases (SMases), whose activities, enzymology, and compartmentalization have been thoroughly reviewed by others (Cremesti et al., 2002;Goni and Alonso, 2002;Kolesnick et al., 2000). A major metabolite of ceramide is ceramide-1-phosphate (C1P, Fig. 1), which is generated through direct phosphorylation of ceramide by ceramide kinase (CERK) (Bajjalieh et al., 1989;Kolesnick and Hemer, 1990). This enzyme was first shown to be confined to the microsomal fraction, but its location in the cytosol has also been reported (Mitsutake et al., 2004). Recently, Chalfant and co-workers demonstrated that CERK utilizes ceramide transported to the trans-Golgi apparatus by the ceramide transport protein (CERT). Of note, down-regulation of CERT by RNA interference resulted in strong inhibition of newly synthesized C1P, suggesting that CERT plays a critical role in C1P formation . However, this observation contrasts with that of Bornancin and...

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Section: C1p Regulates Cell Growth and Deathsupporting

confidence: 80%

Section: C1p Regulates Cell Growth and Deathmentioning

confidence: 90%

Section: C1p Regulates Inflammationmentioning

confidence: 99%

Section: C1p Regulates Cell Growth and Deathmentioning

confidence: 99%

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Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Levi

Meijler

Gómez-Muñoz

et al. 2010

Molecular and Cellular Endocrinology

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“…In addition, CSF-1 increases C1P production and C1P stimulates proliferation through activation of PI3K/Akt, JNK, and ERK1/2 pathways (Fig. 3D) (Gangoiti et al 2008).…”

Section: Proliferationmentioning

confidence: 99%

CSF-1 Receptor Signaling in Myeloid Cells

Stanley

Chiţu

2014

Cold Spring Harbor Perspectives in Biology

634

521

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The CSF-1 receptor (CSF-1R) is activated by the homodimeric growth factors colony-stimulating factor-1 (CSF-1) and interleukin-34 (IL-34). It plays important roles in development and in innate immunity by regulating the development of most tissue macrophages and osteoclasts, of Langerhans cells of the skin, of Paneth cells of the small intestine, and of brain microglia. It also regulates the differentiation of neural progenitor cells and controls functions of oocytes and trophoblastic cells in the female reproductive tract. Owing to this broad tissue expression pattern, it plays a central role in neoplastic, inflammatory, and neurological diseases. In this review we summarize the evolution, structure, and regulation of expression of the CSF-1R gene. We discuss the structures of CSF-1, IL-34, and the CSF-1R and the mechanism of ligand binding to and activation of the receptor. We further describe the pathways regulating macrophage survival, proliferation, differentiation, and chemotaxis downstream from the CSF-1R.

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Lactosylceramide‐Induced Phosphorylation Signaling to Group IVA Phospholipase A₂ via Reactive Oxygen Species in Tumor Necrosis Factor‐α‐Treated Cells

Nakamura

Moriyama

Watanabe

et al. 2017

J of Cellular Biochemistry

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The activity of α-type cytosolic phospholipase A (cPLA α, group IVA PLA ), which releases arachidonic acid (AA), is mainly regulated by the Ca -induced intracellular translocation/attachment of the enzyme to substrate membranes and its phosphorylation. We previously reported that tumor necrosis factor-α (TNFα) stimulated the formation of lactosylceramide (LacCer) in L929 fibroblast cells, and this lipid directly bound with and activated cPLA α [Nakamura et al. [2013] J. Biol. Chem. 288:23264-23272]. We herein investigated the role of phosphorylation signaling in the TNFα/LacCer-induced activation of cPLA α in cells. TNFα-treated L929 cells released AA via the phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cPLA α, while a treatment with LacCer alone released AA in a similar manner. The TNFα-induced responses including release of AA were decreased by the inhibition of LacCer synthesis. The treatment with TNFα and LacCer increased the levels of reactive oxygen species (ROS), and the reduction/scavenging of ROS decreased the phosphorylation cascade and release of AA in TNFα/LacCer-treated L929 cells. In the cell line CHO, the treatment with LacCer stimulated the phosphorylation cascade and release of AA via the formation of ROS. Treatments with the anti-LacCer antibody and 4β-phorbol 12-myristate 13-acetate stimulated the phosphorylation cascade, but did not release AA by itself. When combined with the Ca ionophore A23187, treatments with the anti-LacCer antibody and 4β-phorbol 12-myristate 13-acetate released AA. These results, including our previous findings, showed that LacCer alone simultaneously stimulates two processes to activate cPLA α: a phosphorylation signal and attachment of the enzyme to substrate membranes. J. Cell. Biochem. 118: 4370-4382, 2017. © 2017 Wiley Periodicals, Inc.

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Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase/PKB, JNK and ERK1/2 pathways

Cited by 126 publications

References 40 publications

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

CSF-1 Receptor Signaling in Myeloid Cells

Lactosylceramide‐Induced Phosphorylation Signaling to Group IVA Phospholipase A₂ via Reactive Oxygen Species in Tumor Necrosis Factor‐α‐Treated Cells

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Ceramide 1-phosphate stimulates macrophage proliferation through activation of the PI3-kinase/PKB, JNK and ERK1/2 pathways

Cited by 126 publications

References 40 publications

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

Distinct receptor-mediated activities in macrophages for natural ceramide-1-phosphate (C1P) and for phospho-ceramide analogue-1 (PCERA-1)

CSF-1 Receptor Signaling in Myeloid Cells

Lactosylceramide‐Induced Phosphorylation Signaling to Group IVA Phospholipase A2 via Reactive Oxygen Species in Tumor Necrosis Factor‐α‐Treated Cells

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Lactosylceramide‐Induced Phosphorylation Signaling to Group IVA Phospholipase A₂ via Reactive Oxygen Species in Tumor Necrosis Factor‐α‐Treated Cells