Linked Life Data

17630321

Source:http://linkedlifedata.com/resource/pubmed/id/17630321

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2007-11-16
pubmed:abstractText
Apoptosis of alveolar type II (ATII) cells in response to high-amplitude mechanical stretch represents an important mechanism of ventilation-induced lung injury. Previously, it was demonstrated in an in vitro model that stretch-induced ATII cell apoptosis was prevented by angiotensin-converting enzyme (ACE) inhibitors. This study investigates the mechanism by which ACE inhibitors prevent stretch-induced apoptosis and elucidates the role of bradykinin as an endogenous anti-apoptotic factor. Rat ATII cells cultured on flexible membranes were subjected to cyclic stretch (40 cycles/min; 30% increase in surface area) and compared with static controls. Angiotensinogen, the bradykinin precursor T-kininogen, and bradykinin receptor expression were measured by RT-PCR; Angiotensin II and phosphoinositol 3 OH-kinase (PI3K) activity (as phospho-Akt) were measured by enzyme-linked immunosorbent assay; and Bcl-2 and Bcl-X(L) were measured by Western blot. Stretch did not influence angiotensinogen expression or induce angiotensin II generation. The angiotensin II receptor antagonist saralasin did not prevent stretch-induced apoptosis, whereas ACE inhibitors did. Stretch reduced ATII cell bradykinin release (T-kininogen expression and bradykinin supernatant concentration), and subsequently led to reduced PI3K activity and decreased concentrations of the anti-apoptotic proteins Bcl-2/Bcl-X(L). Bradykinin substitution or addition of keratinocyte or hepatocyte growth factor prevented stretch-induced decrease in PI3K activity and Bcl-2/Bcl-X(L) and reduced stretch-induced apoptosis. Mechanical stretch impairs a constitutively expressed, autocrine anti-apoptotic ATII cell survival signal involving bradykinin-mediated stimulation of the PI3K-Akt-Bcl-2/Bcl-X(L) pathway. Restoration of this pathway prevents stretch-induced apoptosis. This may be beneficial when mechanical ventilation cannot completely avoid alveolar overdistension to maintain oxygenation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
1535-4989
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
37
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
699-705
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:17630321-Angiotensin II, pubmed-meshheading:17630321-Angiotensin II Type 1 Receptor Blockers, pubmed-meshheading:17630321-Animals, pubmed-meshheading:17630321-Apoptosis, pubmed-meshheading:17630321-Biomechanics, pubmed-meshheading:17630321-Bradykinin, pubmed-meshheading:17630321-Enzyme Activation, pubmed-meshheading:17630321-Gene Expression Regulation, pubmed-meshheading:17630321-Hepatocyte Growth Factor, pubmed-meshheading:17630321-Kallikreins, pubmed-meshheading:17630321-Male, pubmed-meshheading:17630321-Mechanotransduction, Cellular, pubmed-meshheading:17630321-Peptidyl-Dipeptidase A, pubmed-meshheading:17630321-Phosphatidylinositol 3-Kinases, pubmed-meshheading:17630321-Proto-Oncogene Proteins c-akt, pubmed-meshheading:17630321-Pulmonary Alveoli, pubmed-meshheading:17630321-Rats, pubmed-meshheading:17630321-Rats, Sprague-Dawley
pubmed:year
2007
pubmed:articleTitle
Stretch-induced alveolar type II cell apoptosis: role of endogenous bradykinin and PI3K-Akt signaling.
pubmed:affiliation
Department of Respiratory Medicine, University of Leipzig, Leipzig, Germany. stefan.hammerschmidt@t-online.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't