The Role of Sphingosine‐1‐Phosphate Activity in Liver Preservation Injury

: Acid ceramidase (AC), the key enzyme of the ceramide metabolic pathway hydrolyzes pro-apoptotic ceramide to sphingosine, which by the action of sphingosine-1-kinase is metabolized to mitogenic sphingosine-1-phosphate. The intracellular level of AC determines ceramide/sphingosine-1-phosphate rheostat which in turn decides the cell fate. The upregulated AC expression during cancerous condition acts as a “double-edged sword” by converting pro-apoptotic ceramide to anti-apoptotic sphingosine-1-phosphate, wherein on one end, the level of ceramide is decreased and on the other end, the level of sphingosine-1-phosphate is increased, thus altogether aggravating the cancer progression. In addition, cancer cells with upregulated AC expression exhibited increased cell proliferation, metastasis, chemoresistance, radioresistance and numerous strategies were developed in the past to effectively target the enzyme. Gene silencing and pharmacological inhibition of AC sensitized the resistant cells to chemo/radiotherapy thereby promoting cell death. The core objective of this review is to explore AC mediated tumour progression and the potential role of AC inhibitors in various cancer cell lines/models.

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Sphingolipids in Ventilator Induced Lung Injury: Role of Sphingosine-1-Phosphate Lyase

International Journal of Molecular Sciences ◽

10.3390/ijms19010114 ◽

2018 ◽

Vol 19 (1) ◽

pp. 114 ◽

Cited By ~ 12

Author(s):

Vidyani Suryadevara ◽

Panfeng Fu ◽

David Ebenezer ◽

Evgeny Berdyshev ◽

Irina Bronova ◽

...

Keyword(s):

Lung Injury ◽

Ventilator Induced Lung Injury ◽

Sphingosine 1 Phosphate

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Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Cancers ◽

10.3390/cancers13133357 ◽

2021 ◽

Vol 13 (13) ◽

pp. 3357

Author(s):

Hongmei Zheng ◽

Sumit Siddharth ◽

Sheetal Parida ◽

Xinhong Wu ◽

Dipali Sharma

Keyword(s):

Breast Cancer ◽

Tumor Microenvironment ◽

Triple Negative Breast Cancer ◽

Triple Negative ◽

Treatment Options ◽

Combined Treatment ◽

High Mobility ◽

Sphingosine 1 Phosphate ◽

Molecular Patterns

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

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Piezo1 mediates angiogenesis through activation of MT1-MMP signaling

AJP Cell Physiology ◽

10.1152/ajpcell.00346.2018 ◽

2019 ◽

Vol 316 (1) ◽

pp. C92-C103 ◽

Cited By ~ 19

Author(s):

Hojin Kang ◽

Zhigang Hong ◽

Ming Zhong ◽

Jennifer Klomp ◽

Kayla J. Bayless ◽

...

Keyword(s):

Shear Stress ◽

Wall Shear Stress ◽

Matrix Metalloproteinase ◽

Matrix Metalloproteinase 2 ◽

Sprouting Angiogenesis ◽

Sphingosine 1 Phosphate ◽

Wall Shear ◽

Membrane Type

Angiogenesis is initiated in response to a variety of external cues, including mechanical and biochemical stimuli; however, the underlying signaling mechanisms remain unclear. Here, we investigated the proangiogenic role of the endothelial mechanosensor Piezo1. Genetic deletion and pharmacological inhibition of Piezo1 reduced endothelial sprouting and lumen formation induced by wall shear stress and proangiogenic mediator sphingosine 1-phosphate, whereas Piezo1 activation by selective Piezo1 activator Yoda1 enhanced sprouting angiogenesis. Similarly to wall shear stress, sphingosine 1-phosphate functioned by activating the Ca2+ gating function of Piezo1, which in turn signaled the activation of the matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase during sprouting angiogenesis. Studies in mice in which Piezo1 was conditionally deleted in endothelial cells demonstrated the requisite role of sphingosine 1-phosphate-dependent activation of Piezo1 in mediating angiogenesis in vivo. These results taken together suggest that both mechanical and biochemical stimuli trigger Piezo1-mediated Ca2+ influx and thereby activate matrix metalloproteinase-2 and membrane type 1 matrix metalloproteinase and synergistically facilitate sprouting angiogenesis.

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Role of Afadin in Vascular Endothelial Growth Factor– and Sphingosine 1-Phosphate–Induced Angiogenesis

Circulation Research ◽

10.1161/circresaha.110.216747 ◽

2010 ◽

Vol 106 (11) ◽

pp. 1731-1742 ◽

Cited By ~ 61

Author(s):

Hideto Tawa ◽

Yoshiyuki Rikitake ◽

Motonori Takahashi ◽

Hisayuki Amano ◽

Muneaki Miyata ◽

...

Keyword(s):

Vascular Endothelial Growth Factor ◽

Growth Factor ◽

Vascular Endothelial ◽

Sphingosine 1 Phosphate ◽

Endothelial Growth Factor

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Sphingosine kinase 2 prevents the nuclear translocation of sphingosine 1-phosphate receptor-2 and tyrosine 416 phosphorylated c-Src and increases estrogen receptor negative MDA-MB-231 breast cancer cell growth: The role of sphingosine 1-phosphate receptor-4

Cellular Signalling ◽

10.1016/j.cellsig.2014.01.023 ◽

2014 ◽

Vol 26 (5) ◽

pp. 1040-1047 ◽

Cited By ~ 17

Author(s):

Jan Ohotski ◽

Hugh Rosen ◽

Robert Bittman ◽

Susan Pyne ◽

Nigel J. Pyne

Keyword(s):

Breast Cancer ◽

Estrogen Receptor ◽

Nuclear Translocation ◽

Sphingosine Kinase ◽

Cancer Cell Growth ◽

Breast Cancer Cell Growth ◽

Sphingosine Kinase 2 ◽

Sphingosine 1 Phosphate ◽

Estrogen Receptor Negative

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The protective role of sphingosine-1-phosphate against the action of the vascular disrupting agent combretastatin A-4 3-O-phosphate

Oncotarget ◽

10.18632/oncotarget.21172 ◽

2017 ◽

Vol 8 (56) ◽

pp. 95648-95661 ◽

Cited By ~ 3

Author(s):

Joanna Shepherd ◽

Matthew Fisher ◽

Abigail Welford ◽

Donald M. McDonald ◽

Chryso Kanthou ◽

...

Keyword(s):

Protective Role ◽

Vascular Disrupting Agent ◽

Sphingosine 1 Phosphate ◽

Vascular Disrupting

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The Sphingolipid Asset Is Altered in the Nigrostriatal System of Mice Models of Parkinson’s Disease

Biomolecules ◽

10.3390/biom12010093 ◽

2022 ◽

Vol 12 (1) ◽

pp. 93

Author(s):

Victor Blokhin ◽

Maria Shupik ◽

Ulyana Gutner ◽

Ekaterina Pavlova ◽

Albert T. Lebedev ◽

...

Keyword(s):

Gene Expression ◽

Parkinson’S Disease ◽

Parkinson's Disease ◽

Sphingolipid Metabolism ◽

Nigrostriatal System ◽

Dopaminergic Cell ◽

Metabolism Enzymes ◽

Clinical Stages ◽

Sphingosine 1 Phosphate

Parkinson’s disease (PD) is a neurodegenerative disease incurable due to late diagnosis and treatment. Therefore, one of the priorities of neurology is to study the mechanisms of PD pathogenesis at the preclinical and early clinical stages. Given the important role of sphingolipids in the pathogenesis of neurodegenerative diseases, we aimed to analyze the gene expression of key sphingolipid metabolism enzymes (ASAH1, ASAH2, CERS1, CERS3, CERS5, GBA1, SMPD1, SMPD2, UGCG) and the content of 32 sphingolipids (subspecies of ceramides, sphingomyelins, monohexosylceramides and sphinganine, sphingosine, and sphingosine-1-phosphate) in the nigrostriatal system in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse models of the preclinical and clinical stages of PD. It has been shown that in PD models, the expression of five of the nine studied genes (CERS1, CERS5, ASAH1, ASAH2, and GBA1) increases but only in the substantia nigra (SN) containing dopaminergic cell bodies. Changes in the expression of enzyme genes were accompanied by an increase in the content of 7 of the 32 studied sphingolipids. Such findings suggest these genes as attractive candidates for diagnostic purposes for preclinical and clinical stages of PD.

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