Dysregulated Sphingolipid Metabolism in Endometriosis
Dysregulated Sphingolipid Metabolism in Endometriosis
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DOI：
10.1210/jc.2014-1340
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发表时间：
2014-10-01
影响因子：
5.8
通讯作者：
Chan, Jerry Kok Yen
中科院分区：
文献类型：
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作者：
Lee, Yie Hou;Tan, Chin Wen;Chan, Jerry Kok Yen
背景资料：在子宫内膜异位症中，子宫内膜外异位病变的建立和存在表明病理性增生的细胞状态发生了改变。鞘脂是生物活性化合物，其生物合成和代谢调节一系列细胞过程，包括增殖、迁移和凋亡。我们证明，异常的鞘脂代谢发生在妇女子宫内膜异位症。方法：靶向质谱测定> 120鞘脂在血清（n = 62），腹腔液（n = 63），子宫内膜组织（n = 14）的妇女和子宫内膜异位症。对子宫内膜组织进行定量RT-PCR和免疫组化，确定鞘脂enzymes.Results的表达水平：鞘脂组学确定了体内积累的许多鞘脂，包括功能拮抗性葡萄糖神经酰胺和神经酰胺在血清和PF的妇女子宫内膜异位症。我们发现在子宫内膜异位症妇女子宫内膜中特异性鞘脂酶，即鞘磷脂合酶1（SMS 1）、鞘磷脂酶3（SMPD 3）和葡糖神经酰胺合酶（GCS）的上调，相应地GlcCer增加，鞘磷脂水平降低，子宫内膜细胞凋亡减少。我们的鞘脂组学方法提供了子宫内膜异位症患者血清、腹腔液和子宫内膜组织中鞘脂代谢通量改变的证据。这些结果为鞘脂和在位子宫内膜在子宫内膜异位症的病理生理机制中的作用提供了新的信息。这些结果也对鞘脂作为潜在生物标志物的使用产生了影响。
Background: In endometriosis, the establishment and subsistence of ectopic lesions outside the endometrium suggest an altered cellular state for pathological hyperplasia. Sphingolipids are bioactive compounds, and their biosynthesis and metabolism modulate a range of cellular processes including proliferation, migration and apoptosis. We demonstrate that aberrations in sphingolipid metabolism occur in women with endometriosis.Methods: Targeted mass spectrometry on > 120 sphingolipids were measured in the sera (n = 62), peritoneal fluid (n = 63), and endometrial tissue (n = 14) of women with and without endometriosis. Quantitative RT-PCR and immunohistochemistry were performed on endometrial tissues determine the expression levels of sphingolipid enzymes.Results: Sphingolipidomics identified the in vivo accumulation of numerous sphingolipids, including the functionally antagonistic glucosylceramides and ceramides in the serum and PF of women with endometriosis. We found upregulation of specific sphingolipid enzymes, namely sphingomyelin synthase 1 (SMS1), sphingomyelinase 3 (SMPD3), and glucosylceramide synthase (GCS) in the endometrium of endometriotic women with corresponding increased GlcCer, decreased sphingomyelin levels, and decreased apoptosis in the endometrium.Conclusions: Our sphingolipidomics approach provided evidence of altered sphingolipid metabolism flux in serum, peritoneal fluid, and endometrial tissue in women with endometriosis. The results provide new information on how sphingolipids and eutopic endometrium may contribute to the pathophysiology of endometriosis. The results also have implications for the use of sphingolipids as potential biomarkers.