Linked Life Data

1675112

Source:http://linkedlifedata.com/resource/pubmed/id/1675112

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
1991-7-16
pubmed:abstractText
Luminal epithelium from mouse small intestine was fractionated into four distinct components ranging from the most differentiated (absorptive epithelial cells, fraction I) to the least differentiated (proliferative crypt cells, fraction IV). Immunoblot analysis of these fractions with monoclonal antibodies to P-glycoprotein, C219, and HYB-241, indicated that the amount of P-glycoprotein increased in cells as they progressed in level of differentiation from crypt to the villar surface of the lumen of the small intestine. P-glycoprotein in these normal intestinal cells functioned as a transporter of vincristine, one of a group of cancer chemotherapeutic agents to which cells can develop multidrug resistance. Transport ability was shown by efflux studies with vincristine as substrate. Efflux increased with differentiation and correlated with the increase in the amount of P-glycoprotein. Fraction I cells effluxed vincristine about seven times more rapidly than fraction IV cells. Efflux of vincristine was almost entirely inhibited from fraction I cells after treatment with antibody HYB-241, which recognizes an external epitope of P-glycoprotein. This finding would appear to demonstrate that P-glycoprotein was directly responsible for at least the majority of efflux of vincristine in these cells. The observed Mr of P-glycoprotein in fraction I cells was 140,000 when cells were solubilized with sodium dodecyl sulfate at room temperature before electrophoresis and immunoblot analysis. When solubilized fraction I protein was heated with 2-mercaptoethanol before electrophoresis, P-glycoprotein was seen by immunochemical procedures as an Mr 50,000-55,000 protein. No Mr 170,000 or 180,000 forms of P-glycoprotein (forms that are found in multidrug-resistant cell lines and are stable to heat or sulhydryl agents) were detected in any fraction of these epithelial cells under the conditions used. Functional P-glycoprotein was, therefore, associated with differentiation of luminal epithelium in small intestine, and the P-glycoprotein produced by these cells may be a type not previously described.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0955-3541
pubmed:author
pubmed:issnType
Print
pubmed:volume
3
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-65
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1991
pubmed:articleTitle
P-glycoprotein content and mediation of vincristine efflux: correlation with the level of differentiation in luminal epithelium of mouse small intestine.
pubmed:affiliation
Laboratory of Cellular and Biochemical Genetics, Memorial Sloan-Kettering Cancer Center, New York, New York 10021.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.