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First published on September 1, 2005; DOI: 10.1124/mol.105.015412

0026-895X/05/6806-1716-1727$20.00
Mol Pharmacol 68:1716-1727, 2005

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Sulfated Polymannuroguluronate, a Novel Anti-AIDS Drug Candidate, Inhibits T Cell Apoptosis by Combating Oxidative Damage of Mitochondria

Benchun Miao, Jing Li, Xueyan Fu, Li Gan, Xianliang Xin, and Meiyu Geng

Department of Pharmacology (B.M., J.L., L.G., X.X., M.G.), Marine Drug and Food Institute, and Department of Food Science and Technology (X.F.), Food Science and Engineering Institute, Ocean University of China, Qingdao, People's Republic of China

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.

Received June 1, 2005; accepted September 1, 2005

Address correspondence to: Dr. Meiyu Geng, Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China, Qingdao 266003, People's Republic of China. E-mail: gengmy{at}mail.ouc.edu.cn






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