title: Staurosporine-induced programmed cell death in Blastocystis occurs independently of caspases and cathepsins and is augmented by calpain inhibition.
abstract: Previous studies have shown that the protozoan parasite Blastocystis exhibits apoptotic features with caspase-like activity upon exposure to a cytotoxic monoclonal antibody or the anti-parasitic drug metronidazole. The present study reports that staurosporine (STS), a common apoptosis inducer in mammalian cells, also induces cytoplasmic and nuclear features of apoptosis in Blastocystis, including cell shrinkage, phosphatidylserine (PS) externalization, maintenance of plasma membrane integrity, extensive cytoplasmic vacuolation, nuclear condensation and DNA fragmentation. STS-induced PS exposure and DNA fragmentation were abolished by the mitochondrial transition pore blocker cyclosporine A and significantly inhibited by the broad-range cysteine protease inhibitor iodoacetamide. Interestingly, the apoptosis phenotype was insensitive to inhibitors of caspases and cathepsins B and L, while calpain-specific inhibitors augmented the STS-induced apoptosis response. While the identities of the proteases responsible for STS-induced apoptosis warrant further investigation, these findings demonstrate that programmed cell death in Blastocystis is complex and regulated by multiple mediators.
authors.affiliation: Laboratory of Molecular and Cellular Parasitology, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore.
authors.forename: Jing
authors.initials: J
authors.lastname: Yin
authors.affiliation: Laboratory of Molecular and Cellular Parasitology, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore.
authors.forename: Josephine
authors.initials: J
authors.lastname: Howe
authors.affiliation: Laboratory of Molecular and Cellular Parasitology, Department of Microbiology, Yong Loo Lin School of Medicine, National University of Singapore, 5 Science Drive 2, Singapore.
authors.forename: Kevin S W
authors.initials: KSW
authors.lastname: Tan
mesh_terms: D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D016844:Blastocystis / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D002154:Calpain / Q000037:antagonists & inhibitors / Q000502:physiology; D020169:Caspases / Q000378:metabolism; D002403:Cathepsins / Q000502:physiology; D057056:Cysteine Proteases / Q000378:metabolism; D015853:Cysteine Proteinase Inhibitors / Q000494:pharmacology; D006023:Glycoproteins / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019311:Staurosporine / Q000494:pharmacology*
chemical_list: D015853:Cysteine Proteinase Inhibitors; D006023:Glycoproteins; C039304:calpain inhibitors; D002403:Cathepsins; D057056:Cysteine Proteases; D002154:Calpain; D020169:Caspases; D019311:Staurosporine