Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation.
Expression and secretion of apoE isoforms in astrocytes and microglia during inflammation.
复制标题
炎症过程中apoE亚型在星形胶质细胞和小胶质细胞中的表达和分泌。
作者：
Lanfranco MF;Sepulveda J;Kopetsky G;Rebeck GW
神经炎症是神经退行性疾病的常见特征，由阿尔茨海默病风险因子载脂蛋白E（APOE）调节。在脑中，apoE蛋白由星形胶质细胞和小胶质细胞合成。我们研究了人APOE（E2，E3和E4）靶向替代小鼠的星形胶质细胞和小胶质细胞的原代培养物。星形胶质细胞分泌两种apoE，而细胞apoE仅由一种组成。在糖蛋白分离过程中，两种形式的分泌型星形胶质细胞apoE都被结合，聚糖的酶促去除使两种形式的apoE收敛为单一形式;因此，两种星形胶质细胞分泌的apoE是差异糖基化的。小胶质细胞仅释放单一种类的apoE，而细胞apoE由两种形式组成;分泌的apoE和两种形式的细胞apoE中的一种被糖基化。我们用内源性（TNFα）或外源性（LPS）促炎刺激处理原代胶质细胞。脂多糖对星形胶质细胞apoE无影响，而APOE 2和APOE 3小胶质细胞则增加apoE的释放; APOE 4小胶质细胞则无影响。与APOE 2和APOE 3小胶质细胞相比，APOE 4小胶质细胞显示出更高的TNFα基线分泌。TNFα处理仅在APOE 4星形胶质细胞中减少apoE的分泌和细胞表达。星形胶质细胞和小胶质细胞产生的apoE种类的模式不受炎症的影响。两种处理后星形胶质细胞中APOE mRNA均未观察到变化。总之，我们的数据表明，星形胶质细胞和小胶质细胞差异表达和分泌糖基化形式的apoE和APOE 4星形胶质细胞和小胶质细胞是缺乏免疫调节相比，APOE 2和APOE 3。1)apoE同种型的移动和分泌在星形胶质细胞和小胶质细胞之间不同，部分基于O-连接聚糖的存在。2)炎症以同种型和细胞特异性方式影响apoE的分泌和表达。
Neuroinflammation is a common feature in neurodegenerative diseases, modulated by the Alzheimer’s disease risk factor, apolipoprotein E (APOE). In the brain, apoE protein is synthesized by astrocytes and microglia. We examined primary cultures of astrocytes and microglia from human APOE (E2, E3 and E4) targeted-replacement mice. Astrocytes secreted two species of apoE, whereas cellular apoE consisted of only one. Both forms of secreted astrocytic apoE were bound during glycoprotein isolation, and enzymatic removal of glycans produced a convergence of the two forms of apoE to a single form; thus, the two species of astrocyte-secreted apoE are differentially glycosylated. Microglia released only a single species of apoE, while cellular apoE consisted of two forms; the secreted apoE and one of the two forms of cellular apoE were glycosylated. We treated the primary glia with either endogenous (TNFα) or exogenous (LPS) pro-inflammatory stimuli. While LPS had no effect on astrocytic apoE, APOE2 and APOE3 microglia increased release of apoE; APOE4 microglia showed no effect. APOE4 microglia showed higher baseline secretion of TNFα compared to APOE2 and APOE3 microglia. TNFα treatment reduced the secretion and cellular expression of apoE only in APOE4 astrocytes. The patterns of apoE species produced by astrocytes and microglia were not affected by inflammation. No changes in APOE mRNA were observed in astrocytes after both treatments. Together, our data demonstrate that astrocytes and microglia differentially express and secrete glycosylated forms of apoE and that APOE4 astrocytes and microglia are deficient in immunomodulation compared to APOE2 and APOE3. 1) Moification and secretion of apoE isoforms differ between astrocytes and microglia, based in part on the presence of O-linked glycans. 2) Inflammation affects apoE secretion and expression in an isoform- and cell-specific manner.
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DOI：
10.3233/jad-200203
发表时间：
2020
期刊：
Journal of Alzheimer's disease : JAD
影响因子：
--
作者：
Hu Y;Meuret C;Go S;Yassine HN;Nedelkov D
通讯作者：
Nedelkov D
影响因子：
4.2
作者：
Elliott, David A.;Tsoi, Kayan;Garner, Brett
通讯作者：
Garner, Brett
影响因子：
16.2
作者：
Foo LC;Allen NJ;Bushong EA;Ventura PB;Chung WS;Zhou L;Cahoy JD;Daneman R;Zong H;Ellisman MH;Barres BA
通讯作者：
Barres BA
影响因子：
5.3
作者：
Cheng X;Zheng Y;Bu P;Qi X;Fan C;Li F;Kim DH;Cao Q
通讯作者：
Cao Q
DOI：
10.1073/pnas.1434398100
发表时间：
2003-09-16
影响因子：
11.1
作者：
Harris, FM;Brecht, WJ;Huang, YD
通讯作者：
Huang, YD