Synergistic action of cord factor and mycobacterial sulfatides on mitochondria.
The mechanism of a synergistic toxicity of 6,6'-dimycoloyl-alpha,alpha'-d-trehalose (cord factor) and 2,3,6,6'-tetraacyl-alpha,alpha'-d-trehalose 2'-sulfate (sulfolipid I) for mice was studied. Sulfolipid I was entirely nontoxic, but it markedly accelerated the lethal toxicity of cord factor for mice. In vivo, sulfolipid I affected neither respiration nor accompanying phosphorylation of mouse liver mitochondria, whereas in vitro, it induced a swelling and disruption of mitochondrial membranes and strongly inhibited mitochondrial oxidative phosphorylation. The effect of sulfolipid I on mitochondrial structure and function in vitro was neutralized by bovine serum albumin and various animal sera, whereas that of cord factor and cord factor plus sulfolipid I was not prevented by bovine serum albumin. The simultaneous injection of cord factor and sulfolipid I caused an intensive fragmentation of mitochondria and a marked decrease in respiratory and phosphorylative activity in mitochondria. These data indicate that sulfolipid I can achieve an effective attack on mitochondria in combination with cord factor in vivo and induces heavier damage in mitochondrial structure and function than that produced by cord factor alone.
D000818:Animals; D004187:Disaccharides / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D006017:Glycolipids / Q000008:administration & dosage / Q000633:toxicity*; D008297:Male; D051379:Mice; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D008933:Mitochondrial Swelling / Q000187:drug effects; D009169:Mycobacterium tuberculosis / Q000032:analysis; D010085:Oxidative Phosphorylation / Q000187:drug effects; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D013464:Sulfuric Acids / Q000008:administration & dosage / Q000633:toxicity; D014199:Trehalose / Q000008:administration & dosage / Q000633:toxicity*
D004187:Disaccharides; D006017:Glycolipids; D013464:Sulfuric Acids; D012710:Serum Albumin, Bovine; D014199:Trehalose