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Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits T cell apoptosis by combating oxidative damage of mitochondria.

Abstract
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.
AuthorsBenchun Miao, Jing Li, Xueyan Fu, Li Gan, Xianliang Xin, Meiyu Geng
JournalMolecular pharmacology (Mol Pharmacol) Vol. 68 Issue 6 Pg. 1716-27 (Dec 2005) ISSN: 0026-895X [Print] United States
PMID16141310 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Anti-HIV Agents
  • Mitochondrial Proteins
  • Polysaccharides
  • Protective Agents
  • Reactive Oxygen Species
  • Sulfates
  • sulfated polymannuroguluronate
  • Adenosine Triphosphate
Topics
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Anti-HIV Agents (pharmacology)
  • Apoptosis (drug effects)
  • Male
  • Membrane Potentials (drug effects)
  • Mitochondria (drug effects, pathology)
  • Mitochondrial Membranes (physiology)
  • Mitochondrial Proteins (drug effects)
  • Oxidative Stress (drug effects)
  • Polysaccharides (pharmacology)
  • Protective Agents
  • Rats
  • Rats, Wistar
  • Reactive Oxygen Species (metabolism)
  • Sulfates
  • T-Lymphocytes (pathology)

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