Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat.

Red Algal Sulfated Galactan Binds and Protects Neural Cells from HIV-1 gp120 and Tat.
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DOI:
10.3390/ph14080714
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发表时间:
2021-07-23
期刊:
Pharmaceuticals (Basel, Switzerland)
影响因子:
--
通讯作者:
Paris JJ
Paris JJ
中科院分区:
其他
文献类型:
--
作者:
Pomin VH;Mahdi F;Jin W;Zhang F;Linhardt RJ;Paris JJ

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四种不同硫酸化聚糖的潜在神经保护能力:来自 Botryocladia occidentalis 的硫酸化半乳聚糖 (BoSG) (MW > 100 kDa)、来自 Lytechinus variegatus 的硫酸化岩藻聚糖 (LvSF) (MW~90 kDa)、高分子量硫酸葡聚糖 (DxS) (MW 100 kDa) 和普通肝素 (UFH) (MW~15 kDa),使用与混合神经胶质细胞共培养的原代小鼠神经元,评估对 HIV-1 蛋白、R5 嗜性糖蛋白 120 (gp120) 和/或转录反式激活剂 (Tat) 的反应。与单独或组合的HIV-1蛋白具有神经毒性的对照处理细胞相比,BoSG是四种测试的硫酸化聚糖中唯一能够对单独或组合的Tat和/或gp120表现出显着的浓度依赖性神经保护作用的一种。基于表面等离子共振的数据表明,BoSG 可以以 nM 浓度结合两种 HIV-1 蛋白,与 UFH 相比,Tat (7.5 × 10−8 M) 优先于 gp120 (3.2 × 10−7 M),而 UFH 则结合 gp120 (8.7 × 10−7 M) 而不是 Tat (5.7 × 10−6 M)。总体而言,这些数据支持这样的观点:从红藻 B. occidentalis 中提取的硫酸化聚糖 (BoSG) 可以通过直接分子相互作用发挥针对 HIV-1 Tat 和 gp120 的神经保护作用。
The potential neuroprotective capacity of four different sulfated glycans: Botryocladia occidentalis-derived sulfated galactan (BoSG) (MW > 100 kDa), Lytechinus variegatus-derived sulfated fucan (LvSF) (MW~90 kDa), high-molecular weight dextran sulfate (DxS) (MW 100 kDa), and unfractionated heparin (UFH) (MW~15 kDa), was assessed in response to the HIV-1 proteins, R5-tropic glycoprotein 120 (gp120) and/or trans-activator of transcription (Tat), using primary murine neurons co-cultured with mixed glia. Compared to control-treated cells in which HIV-1 proteins alone or combined were neurotoxic, BoSG was, among the four tested sulfated glycans, the only one capable of showing significant concentration-dependent neuroprotection against Tat and/or gp120, alone or combined. Surface plasmon resonance-based data indicate that BoSG can bind both HIV-1 proteins at nM concentrations with preference for Tat (7.5 × 10−8 M) over gp120 (3.2 × 10−7 M) as compared to UFH, which bound gp120 (8.7 × 10−7 M) over Tat (5.7 × 10−6 M). Overall, these data support the notion that sulfated glycan extracted from the red alga B. occidentalis, BoSG, can exert neuroprotection against HIV-1 Tat and gp120, potentially via direct molecular interactions.
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