Abrin induces HeLa cell apoptosis by cytochrome c release and caspase activation.
We identified apoptosis as being a significant mechanism of toxicity following the exposure of HeLa cell cultures to abrin holotoxin, which is in addition to its inhibition of protein biosynthesis by N-glycosidase activity. The treatment of HeLa cell cultures with abrin resulted in apoptotic cell death, as characterized by morphological and biochemical changes, i.e., cell shrinkage, internucleosomal DNA fragmentation, the occurrence of hypodiploid DNA, chromatin condensation, nuclear breakdown, DNA single strand breaks by TUNEL assay, and phosphatidylserine (PS) externalization. This apoptotic cell death was accompanied by caspase-9 and caspase-3 activation, as indicated by the cleavage of caspase substrates, which was preceded by mitochondrial cytochrome c release. The broad-spectrum caspase inhibitor, benzyloxycarbonyl-Val-Ala-Asp-fluoromethyl ketone (zVADfmk), prevented abrin-triggered caspase activation and partially abolished apoptotic cell death, but did not affect mitochondrial cytochrome c release. These results suggest that the release of mitochondrial cytochrome c, and the sequential caspase-9 and caspase-3 activations are important events in the signal transduction pathway of abrin-induced apoptotic cell death in the HeLa cell line.
Institute of Virology, College of Life Sciences, Wuhan University, Wuhan 430072, P.R. China.
Xiaoling
X
Qu
Liuting
L
Qing
D000036:Abrin / Q000494:pharmacology*; D000590:Amino Acid Chloromethyl Ketones / Q000378:metabolism; D017209:Apoptosis / Q000502:physiology*; D061945:Caspase Inhibitors; D020169:Caspases / Q000378:metabolism*; D002467:Cell Nucleus / Q000378:metabolism; D048429:Cell Size; D015853:Cysteine Proteinase Inhibitors / Q000378:metabolism; D045304:Cytochromes c / Q000378:metabolism*; D053938:DNA Fragmentation; D004789:Enzyme Activation; D006367:HeLa Cells / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D020287:In Situ Nick-End Labeling
D000590:Amino Acid Chloromethyl Ketones; D061945:Caspase Inhibitors; D015853:Cysteine Proteinase Inhibitors; C096713:benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone; D000036:Abrin; D045304:Cytochromes c; D020169:Caspases