Apolipoprotein M in High Density Lipoprotein Protects Against Astrocyte Apoptosis Induced By Ischemic Insult Via Sphingosine 1-Phosphate Signaling
Abstract Apolipoprotein M (ApoM) has been reported to be contained in high density lipoprotein (HDL) and bound with sphingosine-1-phosphate (S1P). ApoM-associated HDL exerts protective effects against cell death. The aims of the study were to evaluate the effects of ApoM-associated HDL on astrocytes following ischemic insult. Primary cultured mouse astrocytes were treated with oxygen-glucose deprivation (OGD) followed by recovery. The astrocytes underwent apoptosis after treatment with OGD for 4 h and recovery for 24 h. The addition of HDL with ApoM attenuated apoptotic cell death, but HDL without ApoM did not show any effect. Free S1P or ApoM-bound S1P promoted cell survival and inhibited apoptosis. Only S1P receptor 1 (S1PR1) expression was upregulated and blockage of S1PR1 with specific inhibitor or genetic knockdown of S1pr1 abolished the protective effects. In addition, administration of ApoM containing HDL or free S1P induced activation of Akt and Erk in the astrocytes, and pharmacological inhibition of Akt and Erk rescued cell death after OGD treatment. Taken together, ApoM is required for the protective effects of HDL, which depends on delivery of S1P to S1PR1 by ApoM in HDL, indicating ApoM may be a neuroprotective constituent in plasma.