Sphingolipids in cardiovascular and cerebrovascular systems:Pathological implications and potential therapeutic targets  

作　　者：Masahito Kawabori Rachid Kacimi Joel S Karliner Midori A Yenari 

机构地区：[1]Department of Neurology,San Francisco and San Francisco Veterans Affairs Medical Center,University of California,San Francisco,CA 94121,United States [2]Department of Cardiology,VA Medical Center,University of California San Francisco,San Francisco,CA 94121,United States

出　　处：《World Journal of Cardiology》2013年第4期75-86,共12页世界心脏病学杂志（英文版）（电子版）

基　　金：Supported by Grants from the National Institutes of Health (NS40516,to Yenari MA);the Veteran's Merit Award(Yenari MA);the Uehara Foundation(2013 Research Fellowship,to Kawabori M);the National Heart,Lung,and Blood Institute/NHLBI(1P01 HL 68738 and R01 HL 090606 to Karliner JS);Grants to Yenari MA and Karliner JS were administered by the Northern California Institute for Research and Education;supported by resources of the Veterans Affairs Medical Center, San Francisco,California

摘　　要：The sphingolipid metabolites ceramide,sphingosine,and sphingosine-1-phosphate(S1P) and its enzyme sphingosine kinase(SphK) play an important role in the regulation of cell proliferation,survival,inflammation,and cell death.Ceramide and sphingosine usually inhibit proliferation and promote apoptosis,while its metabolite S1P phosphorylated by SphK stimulates growth and suppresses apoptosis.Because these metabolites are interconvertible,it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determine cell fate.The relevance of this "sphingolipid rheostat" and its role in regulating cell fate has been borne out by work in many labs using many different cell types and experimental manipulations.A central finding of these studies is that SphK is a critical regulator of the sphingolipid rheostat,as it not only produces the pro-growth,anti-apoptotic messenger S1P,but also decreases levels of pro-apoptotic ceramide and sphingosine.Activation of bioactive sphingolipid S1P signaling has emerged as a critical protective pathway in response to acute ischemic injury in both cardiac and cerebrovascular disease,and these observations have considerable relevance for future potential therapeutic targets.The sphingolipid metabolites ceramide,sphingosine,and sphingosine-1-phosphate(S1P) and its enzyme sphingosine kinase(SphK) play an important role in the regulation of cell proliferation,survival,inflammation,and cell death.Ceramide and sphingosine usually inhibit proliferation and promote apoptosis,while its metabolite S1P phosphorylated by SphK stimulates growth and suppresses apoptosis.Because these metabolites are interconvertible,it has been proposed that it is not the absolute amounts of these metabolites but rather their relative levels that determine cell fate.The relevance of this "sphingolipid rheostat" and its role in regulating cell fate has been borne out by work in many labs using many different cell types and experimental manipulations.A central finding of these studies is that SphK is a critical regulator of the sphingolipid rheostat,as it not only produces the pro-growth,anti-apoptotic messenger S1P,but also decreases levels of pro-apoptotic ceramide and sphingosine.Activation of bioactive sphingolipid S1P signaling has emerged as a critical protective pathway in response to acute ischemic injury in both cardiac and cerebrovascular disease,and these observations have considerable relevance for future potential therapeutic targets.

关 键 词：SPHINGOLIPIDS Sphingosine-1-phosphate SPHINGOSINE KINASE CERAMIDE KINASE 

分 类 号：R54[医药卫生—心血管疾病] R743[医药卫生—内科学]