Sphingosine-1-phosphate

Sphingosine 1-phosphate is a metabolic product of cell membrane sphingolipids. It is bound to extracellular chaperones, enriched in circulatory fluids and binds to G protein-coupled Sphingosine 1-phosphate receptors (Sphingosine 1-phosphateRs) used for regulating embryonic development, postnatal organ function and disease.^[1]

In vitro, treatment with 200 and 400 μM Sphingosine 1-phosphate in human ovarian cortical samples in dose-dependent decrease in the protein expression of cleaved caspase-3 using western blot and in the number of apoptotic follicles stained positive for cleaved caspase-3 using immunohistochemistry.^[2] In vitro, with 0.1-10 μM Sphingosine 1-phosphate in a concentration-dependent manner evoked action potential (AP) generation by single fibre electrophysiological recordings.^[3] In addition, using Ca2+ imaging experiments, Sphingosine 1-phosphate at 1 μM can elicit a transient increase in intracellular Ca2+ in astrocytes, followed by sustained elevation.^[4]

In vivo, superfusion of 0.001-10 μM Sphingosine 1-phosphate evoked in concentration-dependent manner vasoconstriction in preglomerular microvessels, predominantly afferent arterioles. ^[5] In vivo experiment it shown that injection 10 mg/kg sphingosine 1-phosphate intravenously in mice caused immediate rigor and death. ^[6] In male beagles, treatment with 85 ug/kg Sphingosine 1-phosphate intravenously decreased the formation of Q(s)/Q(t) (32%), and both the presence of protein (72%) and neutrophils (95%) in BAL fluid compared with vehicle controls. However, Sphingosine 1-phosphate increased the LPS-induced systemic production of three inflammatory cytokines, TNF-alpha (6-fold), KC (1.2-fold), and IL-6 (3-fold), without resulting in end-organ dysfunction.^[7]

References:
[1]Cartier A, et al. Sphingosine 1-phosphate: Lipid signaling in pathology and therapy. Science. 2019 Oct 18;366(6463):eaar5551.
[2]Guzel Y, et al. Sphingosine-1-phosphate protects human ovarian follicles from apoptosis in vitro. Eur J Obstet Gynecol Reprod Biol. 2018 Mar;222:19-24.
[3]Patil MJ, et al. Sphingosine-1-phosphate activates mouse vagal airway afferent C-fibres via Sphingosine 1-phosphateR3 receptors. J Physiol. 2019 Apr;597(7):2007-2019.
[4]Shirakawa H, et al. Sphingosine-1-phosphate induces Ca2+ signaling and CXCL1 release via TRPC6 channel in astrocytes. Glia. 2017 Jun;65(6):1005-1016.
[5]Guan Z, et al. Sphingosine-1-phosphate evokes unique segment-specific vasoconstriction of the renal microvasculature. J Am Soc Nephrol. 2014 Aug;25(8):1774-85.
[6]Igarashi Y, et al. Sphingosine 1-phosphate is a blood constituent released from activated platelets, possibly playing a variety of physiological and pathophysiological roles. Acta Biochim Pol. 1998;45(2):299-309.
[7]Szczepaniak WS,et al. Sphingosine 1-phosphate rescues canine LPS-induced acute lung injury and alters systemic inflammatory cytokine production in vivo. Transl Res. 2008 Nov;152(5):213-24.

1-磷酸鞘氨醇是细胞膜鞘脂的代谢产物。它与细胞外伴侣结合,富含循环液,并与 G 蛋白偶联的 1-磷酸鞘氨醇受体 (Sphingosine 1-phosphateRs) 结合,用于调节胚胎发育、产后器官功能和疾病。^[1]

在体外,使用 200 和 400 μM 1-磷酸鞘氨醇处理人卵巢皮质样本时,使用蛋白质印迹可剂量依赖性地降低裂解的 caspase-3 的蛋白表达以及裂解的 caspase 染色呈阳性的凋亡卵泡数量-3 使用免疫组织化学。^[2] 在体外,0.1-10 μM 1-磷酸鞘氨醇以浓度依赖性方式通过单纤维电生理记录诱发动作电位 (AP) 的产生。^{[ 3]} 此外,使用 Ca2+ 成像实验,1 μM 的鞘氨醇 1-磷酸盐可引起星形胶质细胞中细胞内 Ca2+ 的短暂增加,随后持续升高。^[4]

在体内,灌注 0.001-10 μM 1-磷酸鞘氨醇会以浓度依赖性方式引起肾小球前微血管（主要是传入小动脉）中的血管收缩。 ^[5] 体内实验表明,给小鼠静脉注射10 mg/kg鞘氨醇1-磷酸盐可引起立即僵硬和死亡。 ^[6] 在雄性比格犬中,静脉注射 85 ug/kg 鞘氨醇 1-磷酸盐可降低 Q(s)/Q(t) (32%) 的形成,并且蛋白质 ( 72%) 和 BAL 液中的中性粒细胞 (95%) 与载体对照相比。然而,1-磷酸鞘氨醇增加了 LPS 诱导的三种炎性细胞因子 TNF-α（6 倍）、KC（1.2 倍）和 IL-6（3 倍）的全身产生,而没有导致终末器官功能障碍。^[7]