Sphingosine 1-phosphate signaling in ischemia and reperfusion injury

Abstract

Ischemia and reperfusion injury is a complex hemodynamic pathological phenomenon that engages the metabolic to inflammatory machinery in development of disease conditions like heart failure, stroke and acute kidney failure. Target specific therapeutic approaches for ischemia reperfusion injury remains critical despite the extensive studies contributing to the understanding of its pathogenesis. Ischemic or pharmacological conditionings have been long established manipulations to harness the endogenous protective mechanisms against ischemia reperfusion injury that fostered the development of potential therapeutic targets such as sphingolipids signaling. Sphingosine 1-phosphate has been emerged as a crucial metabolite of sphingolipids to regulate the cell survival, vascular integrity and inflammatory cascades in ischemia reperfusion injury. Sphingosine 1-phosphate signaling process has been implicated to downgrade the mitochondrial dysfunction, apoptotic assembly along with upregulation of RISK and SAFE pro-survival pathways. It also regulates the endothelial dysfunction and immune cells behavior to control the vascular permeability and immune cells infiltration at ischemia reperfusion injury site. Targeting the signaling of this single moiety holds the vast potential to extensively influence the detrimental signaling of ischemia reperfusion injury. This review highlights the role and significance of S1P signaling that can be therapeutically exploit to treat ischemia reperfusion injury mediated pathological conditions in different organs.

Keywords: FTY720-p; Heart failure; Ischemia and reperfusion injury; Pre – post conditioning; Sphingosine 1-phosphate; Stroke.