Linked Life Data

10079207

Source:http://linkedlifedata.com/resource/pubmed/id/10079207

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1999-4-15
pubmed:abstractText
We have recently demonstrated mutually inhibitory ATP-dependent transport of dinitrophenyl-S-glutathione (DNP-SG) and doxorubicin by DNP-SG ATPase purified from human erythrocyte membranes (S. Awasthi et al., 1998a,b). Our previous studies indicate a broad substrate specificity for this transport mechanism, including some P-glycoprotein substrates. Present studies were carried out to determine whether colchicine (COL), a classical P-glycoprotein substrate, could be transported by purified human erythrocyte DNP-SG ATPase reconstituted in artificial liposomes. We also investigated whether leukotriene C4 (LTC4), an endogenous proinflammatory glutathione-conjugate derived from arachidonic acid, would inhibit colchicine transport. Uptake of COL was compared in proteoliposomes reconstituted with the purified DNP-SG ATPase as well as control liposomes in the presence or absence of ATP. Increased colchicine uptake was observed upon addition of ATP to proteoliposomes, but not control liposomes. Uptake was linear with respect to the amount of vesicle protein used. Sensitivity to osmolarity was consistent with intravesicular COL accumulation. The ATP-dependent colchicine uptake was sensitive to temperature in a manner consistent with a protein-mediated transport process with activation energy of 7.3 kcal/mol. Time-dependent COL uptake by proteoliposomes in the presence of ATP was consistent with a single compartment model with an apparent rate constant of 0.21 +/- 0.02 min-1. Kinetic studies indicated a saturable behavior with respect to ATP (Km 2.3 +/- 0.7 mM) and colchicine (Km 4.3 +/- 0.2 microM). LTC4 was found to be a competitive inhibitor of COL transport (Kis 16.4 microM). Since DNP-SG ATPase is present in many tissues, it may play an important role in determining colchicine accumulation in cells. Increased LTC4 would tend to increase cellular COL accumulation.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0041-008X
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
155
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
215-26
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1999
pubmed:articleTitle
ATP-Dependent colchicine transport by human erythrocyte glutathione conjugate transporter.
pubmed:affiliation
Department of Internal Medicine, The University of Texas Medical Branch at Galveston, Galveston, Texas, 77555-1067, USA. sawasthi@utmb.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.