Regulation and function of sphingosine kinase 2 in diseases

Dan-Dan Song, Jun-Hao Zhou and Rui Sheng

Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science, Suzhou, China

Offprint requests to: Rui Sheng, Department of Pharmacology and Laboratory of Aging and Nervous Diseases, Soochow University School of Pharmaceutical Science, 199 Ren Ai Road, Suzhou 215123, China. e-mail: sheng_rui@163.com

Summary. Sphingosine kinase functions to phospho-rylate sphingosine to sphingosine 1-phosphate (S1P) to keep balance in the metabolites of sphingolipids. There are two isoforms of sphingosine kinase, sphingosine kinase 1 (SphK1) and sphingosine kinase 2 (SphK2). Although SphK1 and SphK2 share high sequence similarity, SphK2 has distinct distribution, regulation and function. SphK2 is involved in the pathological processes of varieties of diseases including cancer, neurodegenerative disorders, stroke, cardiovascular diseases and inflammation. SphK2 may promote the proliferation of cancer cells and the progression of inflammation. The SphK2/S1P pathway is also involved in the pathogenesis of neurodegenerative disorders and stroke. S1P produced by SphK2 in the nucleus binds to HDACs, which then inhibits histone acetylation and regulates memory. The SphK2 pathway mediates platelet aggregation, thrombosis, cardioprotection and helps to ameliorate hepatic steatosis. This review focuses on the recent advances in research on SphK2 regulation and its potential roles in diseases, highlighting SphK2 may be a novel therapeutic strategy for diseases. Histol Histopathol 33, 433-445 (2018)

Key words: Sphingosine kinase 2, Sphingosine 1-phosphate, Apoptosis, Autophagy, Cancer, Stroke, Neurodegenerative disorders, Preconditioning

DOI: 10.14670/HH-11-939