Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits T cell apoptosis by combating oxidative damage of mitochondria
Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits T cell apoptosis by combating oxidative damage of mitochondria
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DOI：
10.1124/mol.105.015412
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发表时间：
2005-12-01
影响因子：
3.6
通讯作者：
Geng, MY
中科院分区：
文献类型：
--
作者：
Miao, BC;Li, J;Geng, MY
硫酸化聚甘露糖古洛糖醛酸酯（SPMG）作为我国首个抗艾滋病候选药物进入II期临床试验。在此，我们报告SPMG是有效的保护T淋巴细胞凋亡。进一步的研究表明，SPMG显着升高T细胞线粒体膜电位（MMP）;抑制T细胞线粒体细胞色素c（cyto c）的释放;增强线粒体酶复合物I、III和V的活性;随后增加ATP水平和ATP/ADP比率。此外，SPMG在细胞水平上有效抑制线粒体活性氧（ROS）的产生，并在无细胞体系中清除自由基。SPMG的ATP参与和ROS依赖性抗凋亡的分子机制的特点是已经引起了与线粒体输入受体和ADP/ATP载体的T细胞外和内线粒体膜，分别。这些结果可能为SPMG通过保护HIV感染者的T细胞而发挥抗艾滋病作用提供新的思路。
Sulfated polymannuroguluronate (SPMG) has entered the phase II clinical trial as the first anti-AIDS drug candidate in China. Herein, we report that SPMG was effective at protecting T lymphocytes against apoptosis. Further studies indicated that SPMG significantly elevated mitochondrial membrane potential (MMP) of T cells; inhibited mitochondrial release of cytochrome c (cyto c) in T cells; enhanced the activities of mitochondrial enzyme complex I, III, and V; and subsequently increased ATP level and ATP/ADP ratio. In addition, SPMG potently suppressed reactive oxygen species (ROS) generation in mitochondria at cellular level and scavenged free radicals in cell-free system. The molecular mechanism underlying the ATP-involved and ROS-dependent antiapoptosis of SPMG is characterized as having been caused by its engagement with mitochondrial import receptor and ADP/ATP carrier in T-cell outer and inner mitochondrial membrane, respectively. All these might shed new light on the understanding of anti-AIDS functions of SPMG by protecting T cells of persons infected with human immunodeficiency virus.