Ceramide-1-Phosphate, a New Mediator of Development and Survival in Retina Photoreceptors

Miranda, Gisela Edit; Abrahan, Carolina E.; Agnolazza, Daniela L.; Politi, Luis E.; Rotstein, Nora P.

doi:10.1167/iovs.10-7065

Cited by 33 publications

(25 citation statements)

References 52 publications

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“…Moreover, in RP models the structure and function of photoreceptor cells is preserved when CER synthesis is inhibited (Strettoi et al, 2010). SPH is also considered a pro-apoptotic molecule (Abrahan et al, 2010), whereas the phosphorylated forms of SPH and CER (S1P and C1P, respectively) play opposite roles and promote retinal cell survival and division (Miranda et al, 2011, 2009). Overall, SPL metabolism serves as a rheostat that controls cell fate and operates under tight regulation.…”

Section: Introductionmentioning

confidence: 99%

Specific sphingolipid content decrease in Cerkl knockdown mouse retinas

Garanto

Mandal

Egido‐Gabás

et al. 2013

Experimental Eye Research

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Sphingolipids (SPLs) are finely tuned structural compounds and bioactive molecules involved in membrane fluidity and cellular homeostasis. The core sphingolipid, ceramide (CER), and its derivatives, regulate several crucial processes in neuronal cells, among them cell differentiation, cell–cell interactions, membrane conductance, synaptic transmission, and apoptosis. Mutations in Ceramide Kinase-Like (CERKL) cause autosomal recessive Retinitis Pigmentosa and Cone Rod Dystrophy. The presence of a conserved lipid kinase domain and the overall similarity with CERK suggested that CERKL might play a role in the SPL metabolism as a CER kinase. Unfortunately, CERKL function and substrate(s), as well as its contribution to the retinal etiopathology, remain as yet unknown. In this work we aimed to characterize the mouse retinal sphingolipidome by UPLC-TOF to first, thoroughly investigate the SPL composition of the murine retina, compare it to our Cerkl −/− model, and finally assess new possible CERKL substrates by phosphorus quantification and protein-lipid overlay. Our results showed a consistent and notable decrease of the retinal SPL content (mainly ranging from 30% to 60%) in the Cerkl −/− compared to WT retinas, which was particularly evident in the glucosyl/galactosyl ceramide species (Glc/GalCer) whereas the phospholipids and neutral lipids remained unaltered. Moreover, evidence in favor of CERKL binding to GlcCer, GalCer and sphingomyelin has been gathered. Altogether, these results highlight the involvement of CERKL in the SPL metabolism, question its role as a kinase, and open new scenarios concerning its function.

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Section: Introductionmentioning

confidence: 99%

Specific sphingolipid content decrease in Cerkl knockdown mouse retinas

Garanto

Mandal

Egido‐Gabás

et al. 2013

Experimental Eye Research

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“…In this concern, we recently demonstrated that C1P is a potent activator of PI3-K [107]. Other ions such as carbonate, sulfate, fluoride or tetraborate did not significantly affect A-SMase activity in the HOG cell line [106]. Whether C1P and PIP3 bind to the same or different domains of A-SMase remains to be established.…”

Section: Inhibition Of Acid Sphingomyelinasementioning

confidence: 97%

“…These include neutrophils, [98], cerebellar granule cells [99]), A549 lung adenocarcinoma cells [100], and bone marrow-derived macrophages [101]. For example, C1P was found to stimulate neointimal formation via cell proliferation and cell cycle progression in vascular smooth muscle cells [105], and to stimulate proliferation of photoreceptor progenitors (using retina neuronal cultures) [106]. With regards to the mitogenic effect of C1P, we observed that the mechanisms by which this metabolite promotes cell proliferation involves stimulation of the mitogen-activated protein kinases ERK1-2 (Extracellularly regulated kinases 1-2), PI3K/PKB and c-Jun terminal kinase (JNK) [101], as well as translocation and activation of PKC-α [29].…”

Section: Ceramide 1-phosphatementioning

confidence: 99%

Inhibition of Ceramide Metabolism Key Enzymes and its Implication in Cell Physiology and Pathology

Gómez-Muñoz

Ouro

Arana

et al. 2012

CEI

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The simple sphingolipids ceramide, sphingosine, ceramide 1-phosphate and sphingosine 1-phosphate, and their metabolizing enzymes are implicated in the regulation of vital cellular functions, including angiogenesis, cell differentiation, migration, and cell growth and death. These sphingolipids are also involved in the establishment and progression of many illnesses including cardiovascular diseases such as atherosclerosis, or neurodegenerative diseases such as Parkinson's or Alzheimer's diseases, chronic inflammation, and cancer. Therefore, the development of inhibitors of the enzymes that are responsible for the synthesis and degradation of these metabolites may be essential tools for studying normal cell metabolism as well as for establishing new therapeutic strategies for treatment of disease.

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“…Other facts, in addition to the different acyl chain composition of the ceramides, increase the complexity of studying the role of SLs in cell fate: (i) S1P acts not only intracellularly but also as ligand of specific GPCRs (Maceyka et al, ) (Figure B); (ii) other SL metabolites, such as C1P, can also mediate apoptosis or proliferation depending on the cell type (Miranda et al, ; Bini et al, ; Presa et al, ); and (iii) the synthesis of SL and signalling can occur in different cellular compartments (Newton et al, ).…”

Section: Roles Of Bioactive Sls In the Nervous Systemmentioning

confidence: 99%

Crosstalk between sphingolipids and vitamin D3: potential role in the nervous system

Garcia‐Gil

Pierucci

Vestri

et al. 2017

British J Pharmacology

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Sphingolipids are both structural and bioactive compounds. In particular, ceramide and sphingosine 1-phosphate regulate cell fate, inflammation and excitability. 1-α,25-dihydroxyvitamin D3 (1,25(OH) 2 D 3 ) is known to play an important physiological role in growth and differentiation in a variety of cell types, including neural cells, through genomic actions mediated by its specific receptor, and non-genomic effects that result in the activation of specific signalling pathways. 1,25(OH) 2 D 3 and sphingolipids, in particular sphingosine 1-phosphate, share many common effectors, including calcium regulation, growth factors and inflammatory cytokines, but it is still not known whether they can act synergistically. Alterations in the signalling and concentrations of sphingolipids and 1,25(OH) 2 D 3 have been found in neurodegenerative diseases and fingolimod, a structural analogue of sphingosine, has been approved for the treatment of multiple sclerosis. This review, after a brief description of the role of sphingolipids and 1,25(OH) 2 D 3 , will focus on the potential crosstalk between sphingolipids and 1,25(OH) 2 D 3 in neural cells.Abbreviations 1,25(OH) 2 D 3 , 1-α,25-dihydroxyvitamin D3; AD, Alzheimer disease; APP, amyloid precursor protein; Aβ, amyloid β peptide;These Tables list key protein targets and ligands in this article which are hyperlinked to corresponding entries in http://www.guidetopharmacology.org, the common portal for data from the IUPHAR/BPS Guide to PHARMACOLOGY (Southan et al., 2016), and are permanently archived in the Concise Guide to PHARMACOLOGY 2015/16 ( a,b,c,d,e,f Alexander et al., 2015a.

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Ceramide-1-Phosphate, a New Mediator of Development and Survival in Retina Photoreceptors

Cited by 33 publications

References 52 publications

Specific sphingolipid content decrease in Cerkl knockdown mouse retinas

Specific sphingolipid content decrease in Cerkl knockdown mouse retinas

Inhibition of Ceramide Metabolism Key Enzymes and its Implication in Cell Physiology and Pathology

Crosstalk between sphingolipids and vitamin D3: potential role in the nervous system

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