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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
1
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pubmed:dateCreated |
1986-2-19
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pubmed:abstractText |
Cyclosporine A is a noncytotoxic, natural, 11 amino acid cyclic peptide used clinically as an immunosuppressant to prevent organ rejection after transplantation. Cyclosporine A is an in vitro calmodulin antagonist. At the low concentrations required to inhibit calmodulin-dependent phosphodiesterase in vitro, cyclosporine A causes a dramatic alteration in the nuclear morphology of 23% of human peripheral blood mononuclear leukocytes in vitro without loss of viability. The shape of the nucleus changes from ovoid to a distinctive, radially splayed lobulated structure. The changes occur in a dose-dependent manner in 60 min at 37 degrees C. Specific monoclonal antibodies to human leukocytes identify the cells susceptible to nuclear lobulation by cyclosporine A as OKT4 antigen-positive T cell lymphocytes and monocytes. The lobulated nuclei are 2N as determined by flow cytometric measurement of ethidium bromide fluorescence of DNA. The cyclosporine A-induced lobulation of T cell nuclei requires both physiologic temperature and metabolic energy. Although structurally different than cyclosporine A, the calmodulin antagonists R24571 and W-7 [N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide] also produce T cell nuclear lobulations that are indistinguishable from the nuclear lobulations caused by cyclosporine A. These data indicate that nonmitotic structural elements that govern normal nuclear morphology in a subset of mononuclear leukocytes appear to require a calmodulin-mediated process. Cyclosporine A may be a useful noncytotoxic inhibitor of calmodulin-dependent systems that influence nuclear structure and function.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-3885394,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-410154,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6166661,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6238408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6334364,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6365929,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6391148,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6547722,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-6981669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-7022850,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-7122329,
http://linkedlifedata.com/resource/pubmed/commentcorrection/3484481-7192637
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jan
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pubmed:issn |
0021-9525
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
102
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
145-50
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pubmed:dateRevised |
2009-11-18
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pubmed:meshHeading |
pubmed-meshheading:3484481-Antigens, Surface,
pubmed-meshheading:3484481-Calmodulin,
pubmed-meshheading:3484481-Cell Nucleus,
pubmed-meshheading:3484481-Cell Survival,
pubmed-meshheading:3484481-Cyclosporins,
pubmed-meshheading:3484481-Dose-Response Relationship, Drug,
pubmed-meshheading:3484481-Energy Metabolism,
pubmed-meshheading:3484481-Humans,
pubmed-meshheading:3484481-Imidazoles,
pubmed-meshheading:3484481-Monocytes,
pubmed-meshheading:3484481-RNA Processing, Post-Transcriptional,
pubmed-meshheading:3484481-T-Lymphocytes,
pubmed-meshheading:3484481-Temperature,
pubmed-meshheading:3484481-Transcription, Genetic
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pubmed:year |
1986
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pubmed:articleTitle |
Cyclosporine A, an in vitro calmodulin antagonist, induces nuclear lobulations in human T cell lymphocytes and monocytes.
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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