Sphingosine kinase 1 mediates neuroinflammation following cerebral ischemia

Experimental Neurology
Shuli ZhengJian Cheng

Abstract

Sphingosine kinases (Sphks) are the rate-limiting kinases in the generation of sphingosine-1-phosphate, which is a well-established intracellular pro-survival lipid mediator. Sphk2 has been reported to be protective following experimental stroke. We investigated the role of Sphk1 in cerebral ischemia using a mouse middle cerebral artery occlusion (MCAO) model and an in vitro glucose-oxygen deprivation (OGD) model. Sphk expression and activity were assessed in the ischemic brain with quantitative PCR (qPCR), Western blot, immunohistochemistry and enzyme-linked immunosorbent assay (ELISA). Pharmacological and gene knockdown approaches were utilized to investigate the effects of Sphk1 on stroke outcomes. The expression of Sphk1 but not that of Sphk2 was rapidly induced in the cortical penumbra over 96h after MCAO, and the microglia were one of the major cellular sources of Sphk1 induction. Consistently, Sphk activity was enhanced in the cortical penumbra. In contrast to the protective role of Sphk2, pharmacological inhibition and cortical knockdown of Sphk1 reduced infarction at 24 and 96h after reperfusion. Additionally, the Sphk1 inhibitor improved the neurological deficits at 96h after reperfusion. Mechanistically, Sphk1 inhibi...Continue Reading

References

Feb 3, 2005·Journal of Neurochemistry·Klaus van LeyenEng H Lo
Jul 12, 2007·Journal of Neurochemistry·Nicolas BlondeauChristian Waeber
May 20, 2008·Biochimica Et Biophysica Acta·Lauren BryanSheldon Milstien
Aug 12, 2008·Current Drug Targets·Dai ShidaSarah Spiegel
May 28, 2009·Journal of Medicinal Chemistry·Lingkai WongAlirio J Melendez
Aug 1, 2009·Stroke; a Journal of Cerebral Circulation·Bradley K WackerJeffrey M Gidday
Jul 1, 2010·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Jian ChengPatricia D Hurn
Feb 1, 2011·Annals of Neurology·Ying WeiChristian Waeber
May 7, 2011·Nature Reviews. Immunology·Sarah Spiegel, Sheldon Milstien
Aug 30, 2011·Biochemical and Biophysical Research Communications·Waltraud PfeilschifterJosef Pfeilschifter
Oct 8, 2011·Stroke; a Journal of Cerebral Circulation·Lai Ming YungChristian Waeber
Nov 19, 2011·Journal of the American Society of Nephrology : JASN·Sang Wong ParkH Thomas Lee
Feb 9, 2012·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Bradley K WackerJeffrey M Gidday
Apr 25, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kazuhide HayakawaEng H Lo
May 29, 2012·Cell·Scott J DixonBrent R Stockwell
May 4, 2013·The FEBS Journal·Heidi A Neubauer, Stuart M Pitson
Nov 5, 2013·Translational Stroke Research·Yu HasegawaJohn H Zhang
Dec 3, 2013·Progress in Neurobiology·Yu ZhouQing-Wu Yang
Dec 24, 2013·Progress in Neurobiology·Ted Weita LaiYu Tian Wang
Jan 1, 2014·Progress in Neurobiology·Rehana K LeakJun Chen
Jan 11, 2014·Progress in Neurobiology·Fan ChenXunming Ji
Jan 21, 2014·Progress in Neurobiology·Jiao DengLize Xiong
Mar 29, 2014·Journal of Neurochemistry·Yali WangJian Cheng

❮ Previous
Next ❯

Citations

Nov 9, 2016·Neuropharmacology·Sinead O'Sullivan, Kumlesh K Dev
Jan 28, 2017·British Journal of Pharmacology·Mercedes Garcia-GilElisabetta Meacci
Jan 11, 2018·Cell Death & Disease·Xiaoyu WangXuechu Zhen
Aug 21, 2019·Frontiers in Pharmacology·Sara GrassiPaola Giussani
Mar 24, 2016·Inflammation Research : Official Journal of the European Histamine Research Society ... [et Al.]·Manhua LvLiming Zhang
Jan 31, 2019·International Journal of Molecular Sciences·Nicholas Don-DoncowAnja Meissner
Sep 12, 2020·Neuromolecular Medicine·Bhakta Prasad Gaire, Ji Woong Choi
Nov 12, 2020·Cells·Joseph BonicaYusuf A Hannun
Jan 8, 2021·Journal of Cellular Physiology·Xuehui FanGuozhong Li
May 23, 2021·Experimental Eye Research·Natsuko NakamuraMakoto Aihara

❮ Previous
Next ❯

Related Concepts

Related Feeds

Atopic Dermatitis

Atopic dermatitis is a chronic inflammatory genetically determined disease of the skin marked by increased ability to form reagin (IgE), with increased susceptibility to allergic rhinitis and asthma, and hereditary disposition to a lowered threshold for pruritus. Discover the latest research on atopic dermatitis here.

Brain Ischemia

Brain ischemia is a condition in which there is insufficient blood flow to the brain to meet metabolic demand. Discover the latest research on brain ischemia here.