Linked Life Data

17626154

Source:http://linkedlifedata.com/resource/pubmed/id/17626154

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2007-8-31
pubmed:abstractText
In rodent models of obstructive nephropathy, exogenous epidermal growth factor (EGF) attenuates tubule cell death in rats and exacerbates cell death in mice. To identify species differences in EGF receptor (EGFR) regulation and signaling, cell lysates were prepared from rat, mouse, and human proximal tubule cells (PTC) and compared by immunoblot analysis for expression and phosphorylation of Src and EGFR. Frozen kidney tissue was also analyzed. Results indicate mouse PTC have constitutive Src- and EGFR-kinase activities not detected in rat or human PTC. Immunoblots of rat, mouse, and human kidney homogenates confirmed this finding in vivo. Src-specific inhibitor PP2 and EGFR kinase inhibitor AG1478 decreased EGF-induced apoptosis in mouse PTC by 74% (P < 0.001) and 70% (P < 0.001), respectively. Expression of a constitutive Src mutant cDNA in rat PTC rendered cells susceptible to EGF-induced death. EGF decreased stretch-induced apoptosis by 66% (P < 0.001) relative to vehicle control in human PTC, similar to rat PTC response. We conclude that elevated Src activity in mouse tubular cells alters downstream EGFR signaling and increases susceptibility to EGF-induced cell death. The unexpected finding that a therapeutic agent (EGF) in rats is detrimental in mice underscores the importance of determining which animal best represents the response of human kidneys to a given agent.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Sep
pubmed:issn
1931-857X
pubmed:author
pubmed:issnType
Print
pubmed:volume
293
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
F895-903
pubmed:dateRevised
2011-4-28
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Species differences in renal Src activity direct EGF receptor regulation in life or death response to EGF.
pubmed:affiliation
Department of Pediatrics, University of Virginia, Box 801334, 409 Lane Road, Charlottesville, VA 22908, USA. sck3k@virginia.edu
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural