title: Higher level of plasma bioactive molecule sphingosine 1-phosphate in women is associated with estrogen.
abstract: Both sphingosine 1-phosphate (S1P) and estrogen have been documented to play endothelial protective roles. However, it remains unclear whether estrogen could regulate the anabolism of the bioactive molecule S1P and the underlying mechanisms. In this study, 108 healthy participants were separated into three age groups, and their plasma S1P levels were analyzed by liquid chromatography tandem mass spectrometry. Results showed that the plasma S1P levels were significantly higher in women than those in men within the age of 16-55years old and higher in pre-menopausal than post-menopausal women. The experiment in C57 BL/6 mice confirmed the gender difference of plasma S1P level. In vitro study demonstrated that after the stimulation of 17β-estradiol (E2), S1P levels both in EA.hy926 cells and the culture media were increased about 9 and 3 times, respectively; the mRNA expression, the protein level and the activity of sphingosine kinase (SphK) 1, not SphK2, were markedly increased; the mRNA and protein expression of ATP-binding cassette transporter (ABC) C1, G2 and S1P transporter spinster homolog 2 (Spns2) were significantly elevated; furthermore, the mRNA and protein expressions of S1P receptors (S1PRs) 1-2 were increased in a time-dependent manner. This study suggests that E2 markedly improves S1P synthesis by activating SphK1 and induces S1P export via activating ABCC1, G2 and Spns2 from endothelium system, which may consequently lead to the gender difference of plasma S1P in adult human and mouse. The results of this study suggest that E2 may exert its vasculoprotective function by activation of the SphK1-S1P-S1PR signaling axis.
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Shoudong
authors.initials: S
authors.lastname: Guo
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Yu
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Yingjie
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Lei
authors.initials: L
authors.lastname: Zhai
authors.affiliation: The Affiliated Hospital of Taishan Medical University, Taian, 271000, China.
authors.forename: Helou
authors.initials: H
authors.lastname: Li
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Fuyu
authors.initials: F
authors.lastname: Li
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China.
authors.forename: Yujie
authors.initials: Y
authors.lastname: Kan
authors.affiliation: Key Laboratory of Atherosclerosis in Universities of Shandong Province, Institute of Atherosclerosis, Taishan Medical University, Taian, 271000, China. Electronic address: shucunqin@hotmail.com.
authors.forename: Shucun
authors.initials: S
authors.lastname: Qin
mesh_terms: D000293:Adolescent; D000328:Adult; D000818:Animals; D004958:Estradiol / Q000008:administration & dosage*; D004967:Estrogens / Q000097:blood*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D008246:Lysophospholipids / Q000097:blood*; D008297:Male; D051379:Mice; D008875:Middle Aged; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000096:biosynthesis; D017698:Postmenopause / Q000235:genetics / Q000378:metabolism; D017697:Premenopause / Q000235:genetics / Q000378:metabolism; D049349:Receptors, Lysosphingolipid / Q000096:biosynthesis*; D013110:Sphingosine / Q000031:analogs & derivatives* / Q000097:blood; D000099157:Sphingosine Kinase
chemical_list: D004958:Estradiol; D004967:Estrogens; D008246:Lysophospholipids; D017853:Phosphotransferases (Alcohol Group Acceptor); D049349:Receptors, Lysosphingolipid; D013110:Sphingosine; D000099157:Sphingosine Kinase; C060506:sphingosine 1-phosphate
keywords: Estrogen; Liquid chromatography tandem mass spectrometry; S1P transporter spinster homolog 2; Sphingosine 1-phosphate; Sphingosine kinase