Protective Effects of Sphingosine 1-Phosphate (S1P) Analogue and S1P Receptor 1 Ligation in Radiation-Induced Pneumonitis.

2009 ◽  
Author(s):  
X Sun ◽  
B Mathew ◽  
C Evenoski ◽  
L Moreno-Vinasco ◽  
SF Ma ◽  
...  
Keyword(s):  
Protective Effects ◽  
Sphingosine 1 Phosphate ◽  
Radiation Induced ◽  
S1p Receptor

scholarly journals Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury

2021 ◽  
Author(s):  
Jeffrey R. Jacobson
Keyword(s):  
Lung Injury ◽  
Cell Injury ◽  
Inflammatory Responses ◽  
Small Animal ◽  
Protective Effects ◽  
Sphingosine 1 Phosphate ◽  
Radiation Induced ◽  
Injury Models

AbstractRadiation-induced lung injury (RILI) is a potential complication of thoracic radiotherapy that can result in pneumonitis or pulmonary fibrosis and is associated with significant morbidity and mortality. The pathobiology of RILI is complex and includes the generation of free radicals and DNA damage that precipitate oxidative stress, endothelial cell (EC), and epithelial cell injury and inflammation. While the cellular events involved continue to be elucidated and characterized, targeted and effective therapies for RILI remain elusive. Sphingolipids are known to mediate EC function including many of the cell signaling events associated with the elaboration of RILI. Sphingosine-1-phosphate (S1P) and S1P analogs enhance EC barrier function in vitro and have demonstrated significant protective effects in vivo in a variety of acute lung injury models including RILI. Similarly, statin drugs that have pleiotropic effects that include upregulation of EC S1P receptor 1 (S1PR1) have been found to be strongly protective in a small animal RILI model. Thus, targeting of EC sphingosine signaling, either directly or indirectly, to augment EC function and thereby attenuate EC permeability and inflammatory responses, represents a novel and promising therapeutic strategy for the prevention or treatment of RILI.

scholarly journals A Sphingosine-1-Phosphate Receptor Modulator Attenuated Secondary Brain Injury and Improved Neurological Functions of Mice after ICH

2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
T. Bobinger ◽  
T. Bäuerle ◽  
L. Seyler ◽  
S. v Horsten ◽  
S. Schwab ◽  
...  
Keyword(s):  
Brain Injury ◽  
Acute Stage ◽  
Secondary Brain Injury ◽  
Protective Effects ◽  
Receptor Modulator ◽  
Receptor Modulation ◽  
Short Term Study ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
The Brain

Background. Stroke activates the immune system and induces brain infiltration by immune cells, aggravating brain injury. Poststroke immunomodulation via (S1P-)receptor modulation is beneficial; however, the S1P-modulator in clinical use (FTY-720) is unspecific, and undesirable side effects have been reported. Previously, we tested effects of a novel selective S1P-receptor modulator, Siponimod, on ICH-induced brain injury in acute stage of the disease. In the current study, we investigated whether protective effects of Siponimod, evaluated in a short-term study, will protect the brain of ICH animals at long term as well. Methods. 134 C57BL/6N mice were divided into sham and ICH-operated groups. Collagenase model of ICH was employed. ICH animals were divided into Siponimod treated and nontreated. Dose- and time-dependent effects of Siponimod were investigated. Contraplay between development of brain injury and the number of lymphocytes infiltrating the brain was investigated by forelimb placing, T-Maze test, brain water content calculation, MRI scanning, and immunostaining. Results. Depending on the therapeutic strategy, Siponimod attenuated the development of brain edema, decreased ICH-induced ventriculomegaly and improved neurological functions of animals after ICH. It was associated with less lymphocytes in the brain of ICH animals. Conclusion. Siponimod is able to decrease the brain injury and improves neurological functions of animals after ICH.

Endothelial barrier protection by activated protein C through PAR1-dependent sphingosine 1–phosphate receptor-1 crossactivation

Blood ◽  
2005 ◽  
Vol 105 (8) ◽  
pp. 3178-3184 ◽  
Author(s):  
Clemens Feistritzer ◽  
Matthias Riewald
Keyword(s):  
Endothelial Cells ◽  
Protein C ◽  
Activated Protein C ◽  
Sphingosine Kinase ◽  
Receptor Activation ◽  
Endothelial Barrier ◽  
Protective Effects ◽  
Barrier Integrity ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor

AbstractEndothelial cells normally form a dynamically regulated barrier at the blood-tissue interface, and breakdown of this barrier is a key pathogenic factor in inflammatory disorders such as sepsis. Pro-inflammatory signaling by the blood coagulation protease thrombin through protease activated receptor-1 (PAR1) can disrupt endothelial barrier integrity, whereas the bioactive lipid sphingosine 1-phosphate (S1P) recently has been demonstrated to have potent barrier protective effects. Activated protein C (APC) inhibits thrombin generation and has potent anti-inflammatory effects. Here, we show that APC enhanced endothelial barrier integrity in a dual-chamber system dependent on binding to endothelial protein C receptor, activation of PAR1, and activity of cellular sphingosine kinase. Small interfering RNA that targets sphingosine kinase-1 or S1P receptor-1 blocked this protective signaling by APC. Incubation of cells with PAR1 agonist peptide or low concentrations of thrombin (∼ 40 pM) had a similar barrier-enhancing effect. These results demonstrate that PAR1 activation on endothelial cells can have opposite biologic effects, reveal a role for cross-communication between the prototypical barrier-protective S1P and barrier-disruptive PAR1 pathway, and suggest that S1P receptor-1 mediates protective effects of APC in systemic inflammation.

Protective effects of apocynin against ionizing radiation-induced hepatotoxicity in rats

2021 ◽  
pp. 1-8
Author(s):  
Yasir Furkan Cagin ◽  
Hakan Parlakpinar ◽  
Nigar Vardi ◽  
Salih Aksanyar
Keyword(s):  
Ionizing Radiation ◽  
Protective Effects ◽  
Radiation Induced

scholarly journals Mice Deficient in Sphingosine Kinase 1 Are Rendered Lymphopenic by FTY720

2004 ◽  
Vol 279 (50) ◽  
pp. 52487-52492 ◽  
Author(s):  
Maria L. Allende ◽  
Teiji Sasaki ◽  
Hiromichi Kawai ◽  
Ana Olivera ◽  
Yide Mi ◽  
...  
Keyword(s):  
Vascular Development ◽  
Sphingosine Kinase ◽  
Sphingosine Kinase 1 ◽  
Cellular Functions ◽  
Lymphocyte Trafficking ◽  
Signaling Molecule ◽  
Physiological Functions ◽  
Sphingosine 1 Phosphate ◽  
Sphingosine Kinases ◽  
S1p Receptor

Sphingosine-1-phosphate (S1P), a lipid signaling molecule that regulates many cellular functions, is synthesized from sphingosine and ATP by the action of sphingosine kinase. Two such kinases have been identified, SPHK1 and SPHK2. To begin to investigate the physiological functions of sphingosine kinase and S1P signaling, we generated mice deficient in SPHK1.Sphk1null mice were viable, fertile, and without any obvious abnormalities. Total SPHK activity in mostSphk1-/-tissues was substantially, but not completely, reduced indicating the presence of multiple sphingosine kinases. S1P levels in most tissues from theSphk1-/- mice were not markedly decreased. In serum, however, there was a significant decrease in the S1P level. Although S1P signaling regulates lymphocyte trafficking, lymphocyte distribution was unaffected in lymphoid organs ofSphk1-/- mice. The immunosuppressant FTY720 was phosphorylated and elicited lymphopenia in theSphk1null mice showing that SPHK1 is not required for the functional activation of this sphingosine analogue prodrug. The results with theseSphk1null mice reveal that some key physiologic processes that require S1P receptor signaling, such as vascular development and proper lymphocyte distribution, can occur in the absence of SPHK1.

scholarly journals Sphingosine 1-Phosphate (S1P) Receptor Subtypes S1P1and S1P3, Respectively, Regulate Lymphocyte Recirculation and Heart Rate

2004 ◽  
Vol 279 (14) ◽  
pp. 13839-13848 ◽  
Author(s):  
M. Germana Sanna ◽  
Jiayu Liao ◽  
Euijung Jo ◽  
Christopher Alfonso ◽  
Min-Young Ahn ◽  
...  
Keyword(s):  
Heart Rate ◽  
Receptor Subtypes ◽  
Sphingosine 1 Phosphate ◽  
S1p Receptor ◽  
Lymphocyte Recirculation

Ameliorative and protective effects of ginger and its main constituents against natural, chemical and radiation-induced toxicities: A comprehensive review

2019 ◽  
Vol 123 ◽  
pp. 72-97 ◽  
Author(s):  
Muhammad A. Alsherbiny ◽  
Wessam H. Abd-Elsalam ◽  
Shymaa A. El badawy ◽  
Ehab Taher ◽  
Mohamed Fares ◽  
...  
Keyword(s):  
Protective Effects ◽  
Comprehensive Review ◽  
Radiation Induced
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