Ashok Kumar1, Julie D Saba. 1. Children's Hospital Oakland Research Institute (CHORI), Oakland, CA 94609-1673, USA.
Abstract
BACKGROUND: Sphingosine 1-phosphate (S1P) is a bioactive lipid that regulates cell proliferation, survival and migration and plays an essential role in angiogenesis and lymphocyte trafficking. S1P levels in the circulation and tissues are tightly regulated for proper cell functioning, and dysregulation of this system may contribute to the pathophysiology of certain human diseases. Sphingosine phosphate lyase (SPL) irreversibly degrades S1P and thereby acts as a gatekeeper that regulates S1P signaling by modulating intracellular S1P levels and the chemical S1P gradient that exists between lymphoid organs and circulating blood and lymph. However, SPL also generates biochemical products that may be relevant in human disease. SPL has been directly implicated in various physiological and pathological processes, including cell stress responses, cancer, immunity, hematopoietic function, muscle homeostasis, inflammation and development. OBJECTIVE/ METHODS: This review summarizes the current know-ledge of SPL structure, function and regulation, its involvement in various disease states and currently available small molecules known to modulate SPL activity. RESULTS/ CONCLUSION: This review provides evidence that SPL is a potential target for pharmacological manipulation for the treatment of malignant, autoimmune, inflammatory and other diseases.
BACKGROUND:Sphingosine 1-phosphate (S1P) is a bioactive lipid that regulates cell proliferation, survival and migration and plays an essential role in angiogenesis and lymphocyte trafficking. S1P levels in the circulation and tissues are tightly regulated for proper cell functioning, and dysregulation of this system may contribute to the pathophysiology of certain human diseases. Sphingosine phosphate lyase (SPL) irreversibly degrades S1P and thereby acts as a gatekeeper that regulates S1P signaling by modulating intracellular S1P levels and the chemical S1P gradient that exists between lymphoid organs and circulating blood and lymph. However, SPL also generates biochemical products that may be relevant in human disease. SPL has been directly implicated in various physiological and pathological processes, including cell stress responses, cancer, immunity, hematopoietic function, muscle homeostasis, inflammation and development. OBJECTIVE/ METHODS: This review summarizes the current know-ledge of SPL structure, function and regulation, its involvement in various disease states and currently available small molecules known to modulate SPL activity. RESULTS/ CONCLUSION: This review provides evidence that SPL is a potential target for pharmacological manipulation for the treatment of malignant, autoimmune, inflammatory and other diseases.
Authors: Wen-Qi Lai; Anastasia Windy Irwan; Hong Heng Goh; Hwee Siew Howe; David T Yu; Rafael Valle-Oñate; Iain B McInnes; Alirio J Melendez; Bernard P Leung Journal: J Immunol Date: 2008-12-01 Impact factor: 5.422
Authors: Casey W Shuptrine; Reham Ajina; Elana J Fertig; Sandra A Jablonski; H Kim Lyerly; Zachary C Hartman; Louis M Weiner Journal: Cancer Immunol Immunother Date: 2017-08-02 Impact factor: 6.968
Authors: Pramod Upadhyaya; Ashok Kumar; Hoe-Sup Byun; Robert Bittman; Julie D Saba; Stephen S Hecht Journal: Biochem Biophys Res Commun Date: 2012-06-19 Impact factor: 3.575