Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2004-4-22
pubmed:abstractText
Theta-toxin (perfringolysin O) binds to cell surface cholesterol and forms oligomeric pores that cause membrane damage. Both in cytotoxicity and cell survival assays, a mutant Chinese hamster ovary cell line NPC1(-) that lacked Niemann-Pick C1 showed reduced sensitivity to theta-toxin, compared with wild-type (wt) cells. BCtheta is a derivative of theta-toxin that retains cholesterol-binding activity but lacks cytotoxicity. Confocal and electron microscopy revealed the presence of multiple vesicles which bound BCtheta, both on the cell surface and in the extracellular space of these cells. BCtheta binding to raft microdomains was verified by its resistance to 1% Triton X-100 at 4 degrees C and recovery of bound BCtheta in floating low-density fractions on sucrose density gradient fractionation. BCtheta-labeled vesicles were abolished when NPC1(-) cells were depleted of lipoproteins and also when treated with a Rho-associated kinase inhibitor Y-27632. In addition, similar vesicles were observed in wt cells treated with progesterone. In parallel with these results, theta-toxin sensitivity of NPC1(-) cells was increased when cells were depleted of lipoproteins or treated with Y-27632, whereas that of wt cells was decreased by progesterone. Our findings suggest that sequestration of toxin to raft-enriched cell surface vesicles may underlie reduced sensitivity of NPC1-deficient cells to theta-toxin.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Bacterial Toxins, http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Cholesterol, http://linkedlifedata.com/resource/pubmed/chemical/Clostridium perfringens theta-toxin, http://linkedlifedata.com/resource/pubmed/chemical/Hemolysin Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides..., http://linkedlifedata.com/resource/pubmed/chemical/Lipoproteins, LDL, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/NPC1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Progesterone, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/rho-Associated Kinases
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0948-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
121
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
263-72
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:15069562-Animals, pubmed-meshheading:15069562-Bacterial Toxins, pubmed-meshheading:15069562-Carrier Proteins, pubmed-meshheading:15069562-Cell Line, pubmed-meshheading:15069562-Cell Membrane Permeability, pubmed-meshheading:15069562-Cell Survival, pubmed-meshheading:15069562-Cholesterol, pubmed-meshheading:15069562-Drug Resistance, pubmed-meshheading:15069562-Hemolysin Proteins, pubmed-meshheading:15069562-Humans, pubmed-meshheading:15069562-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:15069562-Lipoproteins, LDL, pubmed-meshheading:15069562-Membrane Glycoproteins, pubmed-meshheading:15069562-Membrane Microdomains, pubmed-meshheading:15069562-Microscopy, Electron, pubmed-meshheading:15069562-Progesterone, pubmed-meshheading:15069562-Protein-Serine-Threonine Kinases, pubmed-meshheading:15069562-Transfection, pubmed-meshheading:15069562-rho-Associated Kinases
pubmed:year
2004
pubmed:articleTitle
Reduced sensitivity of Niemann-Pick C1-deficient cells to theta-toxin (perfringolysin O): sequestration of toxin to raft-enriched membrane vesicles.
pubmed:affiliation
Department of Neurobiology, Tottori University Faculty of Medicine, 683-8503, Yonago, Japan.
pubmed:publicationType
Journal Article