Linked Life Data

10666025

Source:http://linkedlifedata.com/resource/pubmed/id/10666025

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-4-14
pubmed:abstractText
Polyamines are essential for cell migration during early mucosal restitution after wounding in the gastrointestinal tract. Activity of voltage-gated K(+) channels (Kv) controls membrane potential (E(m)) that regulates cytoplasmic free Ca(2+) concentration ([Ca(2+)](cyt)) by governing the driving force for Ca(2+) influx. This study determined whether polyamines are required for the stimulation of cell migration by altering K(+) channel gene expression, E(m), and [Ca(2+)](cyt) in intestinal epithelial cells (IEC-6). The specific inhibitor of polyamine synthesis, alpha-difluoromethylornithine (DFMO, 5 mM), depleted cellular polyamines (putrescine, spermidine, and spermine), selectively inhibited Kv1.1 channel (a delayed-rectifier Kv channel) expression, and resulted in membrane depolarization. Because IEC-6 cells did not express voltage-gated Ca(2+) channels, the depolarized E(m) in DFMO-treated cells decreased [Ca(2+)](cyt) as a result of reduced driving force for Ca(2+) influx through capacitative Ca(2+) entry. Migration was reduced by 80% in the polyamine-deficient cells. Exogenous spermidine not only reversed the effects of DFMO on Kv1.1 channel expression, E(m), and [Ca(2+)](cyt) but also restored cell migration to normal. Removal of extracellular Ca(2+) or blockade of Kv channels (by 4-aminopyridine, 1-5 mM) significantly inhibited normal cell migration and prevented the restoration of cell migration by exogenous spermidine in polyamine-deficient cells. These results suggest that polyamine-dependent intestinal epithelial cell migration may be due partially to an increase of Kv1.1 channel expression. The subsequent membrane hyperpolarization raises [Ca(2+)](cyt) by increasing the driving force (the electrochemical gradient) for Ca(2+) influx and thus stimulates cell migration.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0363-6143
pubmed:author
pubmed:issnType
Print
pubmed:volume
278
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
C303-14
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:10666025-Animals, pubmed-meshheading:10666025-Antisense Elements (Genetics), pubmed-meshheading:10666025-Calcium, pubmed-meshheading:10666025-Calcium Channels, pubmed-meshheading:10666025-Cell Movement, pubmed-meshheading:10666025-Cells, Cultured, pubmed-meshheading:10666025-Eflornithine, pubmed-meshheading:10666025-Enzyme Inhibitors, pubmed-meshheading:10666025-Epithelial Cells, pubmed-meshheading:10666025-Gene Expression, pubmed-meshheading:10666025-Image Processing, Computer-Assisted, pubmed-meshheading:10666025-Intestines, pubmed-meshheading:10666025-Kv1.1 Potassium Channel, pubmed-meshheading:10666025-Ornithine Decarboxylase, pubmed-meshheading:10666025-Polyamines, pubmed-meshheading:10666025-Potassium Channels, pubmed-meshheading:10666025-Potassium Channels, Voltage-Gated, pubmed-meshheading:10666025-Rats, pubmed-meshheading:10666025-Spermidine
pubmed:year
2000
pubmed:articleTitle
Role of K(+) channel expression in polyamine-dependent intestinal epithelial cell migration.
pubmed:affiliation
Department of Surgery, University of Maryland School of Medicine, Baltimore, Maryland 21201, USA. jwang@smail.umaryland.edu
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't