The compensatory enrichment of sphingosine -1- phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus.
The compensatory enrichment of sphingosine -1- phosphate harbored on glycated high-density lipoprotein restores endothelial protective function in type 2 diabetes mellitus.
复制标题
糖化高密度脂蛋白上的鞘氨醇-1-磷酸代偿性富集可恢复 2 型糖尿病的内皮保护功能。
DOI：
10.1186/1475-2840-13-82
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发表时间：
2014-04-21
影响因子：
9.3
通讯作者：
Huang Y
中科院分区：
文献类型：
--
作者：
Tong X;Lv P;Mathew AV;Liu D;Niu C;Wang Y;Ji L;Li J;Fu Z;Pan B;Pennathur S;Zheng L;Huang Y
高密度脂蛋白(HDL)的糖基化降低了其诱导内皮细胞环氧合酶-2(COX-2)表达和前列环素-2(PGI-2)释放的能力。高密度脂蛋白的脂质含量，尤其是鞘氨醇-1-磷酸(S1P)在恢复高密度脂蛋白在2型糖尿病(T2 DM)中的保护功能方面是否起到特定的作用尚不清楚。免疫化学技术表明，与糖尿病高密度脂蛋白相比，糖化高密度脂蛋白失去了调节COX-2表达的保护作用。我们证明了糖尿病高密度脂蛋白和糖化高密度脂蛋白的脂类含量，尤其是磷脂含量不同。UPLC-MS/MS检测结果显示，T2 DM组高密度脂蛋白胆固醇结合的S1P水平明显高于对照组(对照组为309.1 ± 13.71pmol/mg比382.1 ± 24.45pmol/mg，P <； 0.05)。此外，实时定量聚合酶链式反应显示外周血中S1P裂解酶和S1P磷酸酶1/2的mRNA水平降低。S1P受体1和3受体拮抗剂(S1PR1/3)可缩小apoHDLPL(含蛋白质组分和磷脂)与糖尿病apoHDLPL(含蛋白质组分和磷脂)之间的功能差异。在糖化高密度脂蛋白上重组不同剂量的S1P，其诱导COX-2表达的功能恢复到与糖尿病高密度脂蛋白相同的水平。S1P重组高密度脂蛋白(RHDL)调节COX-2表达的机制涉及ERK/MAPK-CREB信号通路的磷酸化。高密度脂蛋白上的S1P是恢复其对T2 DM血管内皮细胞保护作用的主要因素。S1P及其受体是改善T2 DM血管功能障碍的潜在治疗靶点。
Glycation of high-density lipoprotein (HDL) decreases its ability to induce cyclooxygenase-2 (COX-2) expression and prostacyclin I-2 (PGI-2) release in endothelial cells. Whether lipid content of HDL, especially sphingosine-1-phosphate (S1P), plays any specific role in restoring the protective function of HDL in type 2 diabetes mellitus (T2DM) is still unknown. Immunochemical techniques demonstrated that glycated HDL loses its protective function of regulating COX-2 expression compared with diabetic HDL. We proved that the lipid content, especially phospholipid content differed between diabetic HDL and glycated HDL. Levels of HDL-c-bound S1P were increased in T2DM compared with control subjects as detected by UPLC-MS/MS (HDL-c-bound S1P in control subjects vs. T2DM: 309.1 ± 13.71 pmol/mg vs. 382.1 ± 24.45 pmol/mg, P < 0.05). Additionally, mRNA levels of S1P lyase enzymes and S1P phosphatase 1/2 were decreased in peripheral blood by real-time PCR. Antagonist of S1P receptor 1 and 3 (S1PR1/3) diminished the functional difference between apoHDL&PL (HDL containing the protein components and phospholipids) and diabetic apoHDL&PL (diabetic HDL containing the protein components and phospholipids). With different doses of S1P reconstituted on glycated HDL, its function in inducing the COX-2 expression was restored to the same level as diabetic HDL. The mechanism of S1P reconstituted HDL (rHDL) in the process of regulating COX-2 expression involved the phosphorylation of ERK/MAPK-CREB signal pathway. S1P harbored on HDL is the main factor which restores its protective function in endothelial cells in T2DM. S1P and its receptors are potential therapeutic targets in ameliorating the vascular dysfunction in T2DM.
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影响因子：
3.7
作者：
Pan B;Ma Y;Ren H;He Y;Wang Y;Lv X;Liu D;Ji L;Yu B;Wang Y;Chen YE;Pennathur S;Smith JD;Liu G;Zheng L
通讯作者：
Zheng L
影响因子：
6.5
作者：
Baranowski, Marcin;Blachnio-Zabielska, Agnieszka;Gorski, Jan
通讯作者：
Gorski, Jan
影响因子：
158.5
作者：
Barter, Philip;Gotto, Antonio M.;Fruchart, Jean-Charles
通讯作者：
Fruchart, Jean-Charles
影响因子：
15.9
作者：
JAFFE, EA;NACHMAN, RL;MINICK, CR
通讯作者：
MINICK, CR
DOI：
10.1161/atvbaha.107.145672
发表时间：
2007-08-01
影响因子：
8.7
作者：
Kontush, Anatol;Therond, Patrice;Chapman, M. John
通讯作者：
Chapman, M. John