Elevated concentrations of sphingosylphosphorylcholine in cerebrospinal fluid after subarachnoid hemorrhage: A possible role as a spasmogen

Kurokawa, Tetsu; Yumiya, Yasunobu; Fujisawa, Hironori; Shirao, Satoshi; Kashiwagi, Shiro; Sato, Masafumi; Kishi, Hiroko; Miwa, Saori; Mogami, Kimiko; Kato, Shoichi; Akimura, Tatsuo; Soma, Masaaki; Ogasawara, Kuniaki; Ogawa, Akira; Kobayashi, Sei; Suzuki, Michiyasu

doi:10.1016/j.jocn.2009.01.010

Cited by 22 publications

(19 citation statements)

References 18 publications

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“…A recent clinical study has shown that in patients who have developed SAH, the concentration of SPC in the cerebral spinal fluid is significantly increased B17-fold after 7 days (Kurokawa et al, 2009). This provides direct evidence that SPC is elevated in SAH and could therefore contribute to vasospasm.…”

Section: Discussionmentioning

confidence: 99%

Sphingosylphosphorylcholine is a Proinflammatory Mediator in Cerebral Arteries

Wirrig

Hunter

Mathieson

et al. 2010

J Cereb Blood Flow Metab

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Inflammation has an important function in the development of cerebral vasospasm after subarachnoid hemorrhage (SAH); however, the mediators of this inflammatory response have not been clearly identified. In this study, we have investigated the potential function of two sphingolipids, which occur naturally in plasma and serum, sphingosylphosphorylcholine (SPC) and sphingosine 1-phosphate (S1P), to act as proinflammatory mediators in cerebral artery vascular smooth muscle (VSM) cells. In rat cerebral arteries, SPC but not S1P activated p38 mitogen-activated protein kinase (MAPK). Using transcription factor arrays, two proinflammatory transcription factors activated by SPC in cerebral arteries were identified-nuclear factor-jB and CCAAT-enhancerbinding protein. Both these transcription factors were activated by SPC in a p38MAPK-dependent manner. To determine whether this contributed to vascular inflammation, an inflammatory protein array was performed, which showed that SPC increased release of the chemokine monocyte chemoattractant protein-1 (MCP-1) in cultured rat VSM cells. This increase in MCP-1 expression was confirmed in cerebral arteries. The S1P did not increase MCP-1 release. Taken together, our results suggest that SPC, but not S1P, can act as a proinflammatory mediator in cerebral arteries. This may contribute to inflammation observed after SAH and may be part of the initiating event in vasospasm.

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Section: Discussionmentioning

confidence: 99%

Sphingosylphosphorylcholine is a Proinflammatory Mediator in Cerebral Arteries

Wirrig

Hunter

Mathieson

et al. 2010

J Cereb Blood Flow Metab

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“…Further, SPC cerebrospinal fluid (CSF) levels are elevated in SAH patients. (32, 37, 38, 176) Moreover, sphingolipids and CSF ceramide alterations after SAH have also been detected and correlate with clinical outcome. In the CSF of patients with SAH, ceramide is increased and an activation of sphingomyelinae (ASMase), S1P-lyase, and glucosylceramide synthase (GCS) lead to an alteration in the production of protective (S1P) in favor of deleterious (Ceramide) sphingolipids.…”

Section: Stroke and The Sphingolipid Pathwaymentioning

confidence: 99%

“…It has effects on cell proliferation, migration, differentiation, metabolism and cell death in many systems including the cardiovascular system, immune system, central nervous system and skin. (14, 15) It is elevated in some pathological conditions(32–37) and was recently discovered as a pro-inflammatory mediator in cerebral arteries. (38) This, combined with previous evidence on a correlation with post-SAH vasospasm,(32, 37) makes SPC a promising novel target in stroke worthy of further investigation.…”

Section: The Sphingolipid Pathwaymentioning

confidence: 99%

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Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets

Sun

Keep

Hua

et al. 2016

Transl. Stroke Res.

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Sphingolipids are a series of cell membrane derived lipids which act as signaling molecules and play a critical role in cell death and survival, proliferation, recognition and migration. Sphingosine 1 phosphate acts as a key signaling molecule and regulates lymphocyte trafficking, glial cell activation, vasoconstriction, endothelial barrier function and neuronal death pathways which plays a critical role in numerous neurological conditions. Stroke is a second leading cause of death all over the world and effective therapies are still in great demand, including ischemic stroke and hemorrhagic stroke as well as the post stroke repair. Significantly, sphingolipid activities change after stroke and correlate with stroke outcome, which has promoted efforts to testify whether sphingolipid pathway could be a novel therapeutic target in stroke. Sphingolipid metabolic pathway, the connection between the pathway and stroke, as well as therapeutic interventions to manipulate the pathway to reduce stroke-induced brain injury are discussed in this review.

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“…Increased levels of SPC are found in atopic dermatitis, Niemann-Pick disease (NPD), and malignant ascites of patients with tumors [15][16][17]. SPC induces the scratching response in mice via degranulation of mast cells and is also a proinflammatory mediator in cerebral arteries [18][19][20].…”

Section: Introductionmentioning

confidence: 99%

Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation

Kim

Kang

Kim

et al. 2016

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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Sphingosylphosphorylcholine (SPC) participates in several cellular processes including metastasis. SPC induces keratin reorganization and regulates the viscoelasticity of metastatic cancer cells including PANC-1 cancer cells leading to enhanced migration and invasion. The role of SPC and the relevant mechanism in invasion of breast cell are as yet unknown. SPC dose-dependently induces invasion of breast cancer cells or breast immortalized cells. Reverse transcription polymerase chain reaction and Western blot analyses of MCF10A and ZR-75-1 cells indicated that SPC induces expression and secretion of matrix metalloproteinase-3 (MMP3). From online KMPLOT, relapse free survival is high in patients having low MMP3 expressed basal breast cancer (n=581, p=0.032). UK370106 (MMP3 inhibitor) or gene silencing of MMP3 markedly inhibited the SPC-induced invasion of MCF10A cells. An extracellular signal-regulated kinase (ERK) inhibitor, PD98059, significantly suppressed the secretion and the gelatinolytic activity of MMP3, and invasion in MCF10A cells. Over-expression of ERK1 and ERK2 promoted both the expression and secretion of MMP3. In contrast, gene silencing of ERK1 and ERK2 attenuated the secretion of MMP3 in MCF10A cells. The effects of SPC-induced MMP3 secretion on β-catenin and TCF/lymphoid enhancer factor (LEF) promoter activity were examined since MMP3 indirectly activates canonical Wnt signaling. SPC induced translocation of β-catenin to nucleus and increased TCF/LEF promoter activity. These events were suppressed by UK370106 or PD98059. Wnt inhibitor, FH535 inhibited SPC-induced MMP3 secretion and invasion. Taken together, these results suggest that SPC induces MMP3 expression and secretion via ERK leading to Wnt activation.

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Elevated concentrations of sphingosylphosphorylcholine in cerebrospinal fluid after subarachnoid hemorrhage: A possible role as a spasmogen

Cited by 22 publications

References 18 publications

Sphingosylphosphorylcholine is a Proinflammatory Mediator in Cerebral Arteries

Sphingosylphosphorylcholine is a Proinflammatory Mediator in Cerebral Arteries

Critical Role of the Sphingolipid Pathway in Stroke: a Review of Current Utility and Potential Therapeutic Targets

Novel effects of sphingosylphosphorylcholine on invasion of breast cancer: Involvement of matrix metalloproteinase-3 secretion leading to WNT activation

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