An additional mechanism of ribosome-inactivating protein cytotoxicity: degradation of extrachromosomal DNA.
Inhibition of protein synthesis by cleavage of the N-glycosidic bond of a specific adenine of 28 S rRNA has been accepted as the mechanism by which plant ribosome-inactivating proteins (RIPs) cause cytotoxicity. The cytotoxic action of gelonin on Plasmodium falciparum malaria parasites appears to occur by a different mechanism. Parasite intoxication, which is manifested by mitochondrial dysfunction and lack of nucleic acid synthesis in the erythrocytic cycle following exposure to the toxin, is caused by the elimination of the parasite 6 kb extrachromosomal (mitochondrial) DNA. This is the first report which demonstrates that the DNA-damaging activities of RIPs observed in vitro can contribute to their cytotoxicity.
Nicolas
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Department of Pathology, Anatomy and Cell Biology, Jefferson Medical College, 1020 Locust St., Philadelphia, PA 19107, USA.
Goodyer
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Taraschi
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D000818:Animals; D004249:DNA Damage; D004272:DNA, Mitochondrial / Q000187:drug effects*; D016054:DNA, Protozoan / Q000096:biosynthesis / Q000187:drug effects*; D004912:Erythrocytes / Q000469:parasitology; D006801:Humans; D016778:Malaria, Falciparum / Q000097:blood; D010940:Plant Proteins / Q000633:toxicity*; D010963:Plasmodium falciparum / Q000187:drug effects* / Q000502:physiology*; D011500:Protein Synthesis Inhibitors / Q000633:toxicity*; D016053:RNA, Protozoan / Q000096:biosynthesis; D012339:RNA, Ribosomal, 28S / Q000096:biosynthesis; D054789:Ribosome Inactivating Proteins, Type 1; D012270:Ribosomes / Q000187:drug effects*
D004272:DNA, Mitochondrial; D016054:DNA, Protozoan; D010940:Plant Proteins; D011500:Protein Synthesis Inhibitors; D016053:RNA, Protozoan; D012339:RNA, Ribosomal, 28S; D054789:Ribosome Inactivating Proteins, Type 1; C025674:GEL protein, Gelonium multiflorum