The roles of sphingosine kinases in skin aging.
The roles of sphingosine kinases in skin aging.
复制标题
鞘氨醇激酶在皮肤衰老中的作用。
DOI：
10.1016/j.jid.2018.06.192
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发表时间：
2019
影响因子：
6.5
通讯作者：
Takabe K
中科院分区：
文献类型：
--
作者：
Aoki M;Aoki H;Mukhopadhyay P;Katsuta E;Takabe K
鞘脂素-1-磷酸（S1P）是神经酰胺的生物活性代谢物，神经酰胺是鞘脂的基本单位（Aoki et al., 2016）。S1P参与细胞存活、凋亡、血管生成和免疫（Proia and Hla, 2015）。神经酰胺被神经酰胺酶降解为鞘氨醇，鞘氨醇被鞘氨醇激酶1 （SphK1）和2 （SphK2）磷酸化为S1P （Takabe and Spiegel, 2014）。SphK1在细胞质中转运到质膜生成S1P，而SphK2在细胞核中起作用（Studer et al., 2012）。SphK2形成的S1P结合并抑制组蛋白去乙酰化酶HDAC1和HDAC2，调节炎症和代谢基因表达（Hait et al., 2009）。晚期糖基化终产物（AGEs）影响细胞外基质的更新，AGEs受体（RAGE）通过激活NF-κB和诱导I型胶原引起慢性炎症（Serban等，2016）（Peng等，2016）。胶原I是皮肤中最丰富的结构蛋白，是皮肤老化的标志（Varani et al., 2002）。研究表明，暴晒皮肤的成纤维细胞、树形细胞和角质形成细胞中RAGE表达上调，AGEs和肿瘤坏死因子-α增加RAGE表达（Lohwasser et al., 2006）。因此，AGE-RAGE相互作用与皮肤老化过程有关。
Sphingosine-1-phosphate (S1P) is a bioactive metabolite of ceramide, which is the basic unit of sphingolipids (Aoki et al., 2016). S1P is involved in cellular survival, apoptosis, vasculogenesis, and immunity (Proia and Hla, 2015). Ceramide is degraded by ceramidases to sphingosine, and sphingosine is phosphorylated by sphingosine kinases 1 (SphK1) and 2 (SphK2) to S1P (Takabe and Spiegel, 2014). SphK1 is in the cytoplasm, and translocates to the plasma membrane to generate S1P, whereas SphK2 acts in the nucleus (Studer et al., 2012). S1P formed by SphK2 binds and inhibits the histone deacetylases, HDAC1 and HDAC2, and regulates inflammatory and metabolic gene expression (Hait et al., 2009).Advanced glycation end products (AGEs) affect extracellular matrix turnover, and the receptor of AGEs (RAGE) evokes chronic inflammation (Serban et al., 2016) by activating NF-κB and inducing collagen I (Peng et al., 2016). Collagen I is the most abundant structural protein in the skin and is indicative of skin aging (Varani et al., 2002). It has been shown that RAGE is up-regulated in fibroblasts, dendrocytes, and keratinocytes in sun-exposed skin and that AGEs and tumor necrosis factor-α increase RAGE expression (Lohwasser et al., 2006). Thus, AGE-RAGE interaction is implicated in the process of skin aging.