Sulfated polymannuroguluronate, a novel anti-AIDS drug candidate, inhibits T cell apoptosis by combating oxidative damage of mitochondria.
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.
Miao
Benchun
B
Department of Pharmacology, Marine Drug and Food Institute, Ocean University of China, Qingdao 266003, People's Republic of China.
Li
Jing
J
Fu
Xueyan
X
Gan
Li
L
Xin
Xianliang
X
Geng
Meiyu
M
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects / Q000473:pathology*; D051336:Mitochondrial Membranes / Q000502:physiology; D024101:Mitochondrial Proteins / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects*; D011134:Polysaccharides / Q000494:pharmacology*; D020011:Protective Agents; D051381:Rats; D017208:Rats, Wistar; D017382:Reactive Oxygen Species / Q000378:metabolism; D013431:Sulfates; D013601:T-Lymphocytes / Q000473:pathology*
D019380:Anti-HIV Agents; D024101:Mitochondrial Proteins; D011134:Polysaccharides; D020011:Protective Agents; D017382:Reactive Oxygen Species; D013431:Sulfates; C489185:sulfated polymannuroguluronate; D000255:Adenosine Triphosphate