Novel neurotrophic effects of sphingosylphosphorylcholine in cerebellar granule neurons and in PC12 cells

Konno, Naoko; Nakamura, Ayako; Ikeno, Yutaka; Cheon, So-hyun; Kitamoto, Katsuhiko; Arioka, Manabu

doi:10.1016/j.bbrc.2007.09.121

Cited by 5 publications

(3 citation statements)

References 18 publications

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“…In addition, we have recently reported that another choline‐containing lysophospholipid, sphingosylphosphorylcholine (SPC), also rescues CGNs from apoptosis (Konno et al,2007). The structural similarity between LPC and SPC suggests that these lysophospholipids act through similar mechanisms, but in this case again the receptor and the downstream signaling pathway evoked still remain elusive.…”

Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death

Ikeno

Cheon

Konno

et al. 2008

J of Neuroscience Research

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Cultured cerebellar granule neurons (CGNs) undergo apoptosis when deprived of depolarizing stimulation and provide an in vitro model system with which to study the effects of neurotrophic substances. Our previous results showed that secretory phospholipases A(2) (sPLA(2)s) protect CGNs from apoptotic cell death under the nondepolarizing condition. In this study, we further analyzed the mechanism whereby sPLA(2) exhibits this effect. Among the primary metabolites of sPLA(2) tested, lysophosphatidylcholine (LPC), but not other lysophospholipids, remarkably rescued CGNs from apoptosis. In contrast, neither arachidonic nor oleic acids displayed neurotrophic effect. Release of LPC into the culture media occurred in response to sPLA(2) treatment, and degradation or sequestration of LPC attenuated the survival-promoting effects of sPLA(2) and LPC. The neurotrophic effect of LPC required the presence of extracellular Ca(2+) and L-type Ca(2+) channel activity, suggesting that Ca(2+) influx across the plasma membrane is evoked by LPC. sPLA(2)- or LPC-induced promotion of CGN survival was suppressed by inhibitors of protein kinase A and phospholipase C, suggesting that they play a role in mediating survival-promoting signal of sPLA(2). The results presented here demonstrate a novel, unexpected neurotrophin-like effect of LPC in the central nervous system.

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Section: Discussionmentioning

confidence: 99%

Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death

Ikeno

Cheon

Konno

et al. 2008

J of Neuroscience Research

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“…Recently, Murch et al [26] showed that lysophosphatidylcholine (LPC) and SPC reduced organ injury and dysfunction in rodent models. In the nervous system the neurotrophic effects of SPC have been reported, but the mechanism is rarely known [27]. In this present study, we investigated whether SPC, phosphocholine (PC) and other lysophospholipids (LPs) like LPC, lysophosphatidic acid (LPA), S1P, affect Ab production in PC12 cell line which represents a useful in vitro model for neurodegenerative disorders.…”

Section: Introductionmentioning

confidence: 98%

Sphingosylphosphorylcholine Attenuated β–Amyloid Production by Reducing BACE1 Expression and Catalysis in PC12 Cells

Lee

et al. 2011

Neurochem Res

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Abnormal accumulation of β-amyloid (Aβ) is the main characteristic of Alzheimer's disease (AD) brain and Aβ peptides are generated from proteolytic cleavages of amyloid precursor protein (APP) by β-site APP-converting enzyme 1 (BACE1) and presenilin 1 (PS1). Sphingosylphosphorylcholine (SPC), a choline-containing sphingolipid, showed suppressive effect on Aβ production in PC12 cells which stably express Swedish mutant of amyloid precursor protein (APPsw). SPC (> 3 μM) significantly lowered the accumulation of Aβ40/42 and the expression of BACE1. However, the transcriptions of other APP processing enzymes like ADAM10 and PS1 were not affected by the SPC addition. Meanwhile, phosphocholine (PC) or other lysophospholipids, such as lysophosphatidylcholine (LPC), lysophosphatidic acid (LPA), sphingosyl-1-phosphate (S1P), did not alter BACE1 expression. Down-regulatory effect of SPC on BACE1 expression appeared to be mediated by NF-κB which is known to suppress the trans-activation of BACE1 promoter in PC12 cells. Here, the nuclear tanslocation of NF-κB was enhanced by SPC treatment in immune-fluorescent image analysis and NF-κB reporter assay. Furthermore, the catalytic activities of BACE1 and BACE2 were dose-dependently inhibited by SPC displaying IC₅₀ values of 2.79 μM and 12.05 μM, respectively. Overall, these data suggest that SPC has the potential to ameliorate Aβ pathology in neurons by down-regulating the BACE1-mediated amyloidogenic pathway.

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“…In the immune system, cell surface S1P(1) receptors transduce the rapid, transient effects of extracellular S1P on T- and B-lymphocyte trafficking, promote early T-cell migration to tissue sites of immune responses, and regulate T-cell proliferation and secretion of numerous cytokines [ 1 , 3 ]. S1P receptors are also found on all cell types in the CNS, and the effects of S1P on neurons [ 4 ], astrocytes [ 5 , 6 ], oligodendrocytes [ 7 ], and microglia [ 8 , 9 ] are highly cell-type specific. For example, S1P is a chemoattractant for neural precursor cells and is proposed to direct migration of neurons to sites of injury [ 10 ].…”

Section: Introductionmentioning

confidence: 99%

Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis

Kułakowska

Byfield

Żendzian-Piotrowska

et al. 2014

J Neuroinflammation

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BackgroundTick-borne encephalitis (TBE) is a serious acute central nervous system infection that can result in death or long-term neurological dysfunctions. We hypothesize that changes in sphingosine-1-phosphate (S1P) concentration occur during TBE development.MethodsS1P and interleukin-6 (IL-6) concentrations in blood plasma and cerebrospinal fluid (CSF) were measured using HPLC and ELISA, respectively. The effects of S1P on cytoskeletal structure and IL-6 production were assessed using rat astrocyte primary cultures with and without addition of plasma gelsolin and the S1P receptor antagonist fingolimod phosphate (FTY720P).ResultsWe report that acute inflammation due to TBE virus infection is associated with elevated levels of S1P and IL-6 in the CSF of infected patients. This elevated concentration is observed even at the earliest neurologic stage of disease, and may be controlled by glucocorticosteroid anti-inflammatory treatment, administered to patients unresponsive to antipyretic drugs and who suffer from a fever above 39°C. In vitro, treatment of confluent rat astrocyte monolayers with a high concentration of S1P (5 μM) results in cytoskeletal actin remodeling that can be prevented by the addition of recombinant plasma gelsolin, FTY720P, or their combination. Additionally, gelsolin and FTY720P significantly decreased S1P-induced release of IL-6.ConclusionsTBE is associated with increased concentration of S1P and IL-6 in CSF, and this increase might promote development of inflammation. The consequences of increased extracellular S1P can be modulated by gelsolin and FTY720P. Therefore, blocking the inflammatory response at sites of infection by agents modulating S1P pathways might aid in developing new strategies for TBE treatment.

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Novel neurotrophic effects of sphingosylphosphorylcholine in cerebellar granule neurons and in PC12 cells

Cited by 5 publications

References 18 publications

Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death

Lysophosphatidylcholine protects cerebellar granule neurons from apoptotic cell death

Sphingosylphosphorylcholine Attenuated β–Amyloid Production by Reducing BACE1 Expression and Catalysis in PC12 Cells

Increased levels of sphingosine-1-phosphate in cerebrospinal fluid of patients diagnosed with tick-borne encephalitis

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