Linked Life Data

12185080

Source:http://linkedlifedata.com/resource/pubmed/id/12185080

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
46
pubmed:dateCreated
2002-11-11
pubmed:abstractText
In the pulmonary artery isolated from 1-week hypoxia-induced pulmonary hypertensive rats, endothelial NO production stimulated by carbachol was decreased significantly in in situ visualization using diaminofluorescein-2 diacetate and also in cGMP content. This change was followed by the decrease in carbachol-induced endothelium-dependent relaxation. Protein expression of endothelial NO synthase (eNOS) and its regulatory proteins, caveolin-1 and heat shock protein 90, did not change in the hypoxic pulmonary artery, indicating that chronic hypoxia impairs eNOS activity at posttranslational level. In the hypoxic pulmonary artery, the increase in intracellular Ca(2+) level stimulated by carbachol but not by ionomycin was reduced. We next focused on changes in Ca(2+) sensitivity of the eNOS activation system. A morphological study revealed atrophy of endothelial cells and a peripheral condensation of eNOS in hypoxic endothelial cells preserving co-localization between eNOS and Golgi or plasma membranes. However, eNOS was tightly coupled with caveolin-1, and was dissociated from heat shock protein 90 or calmodulin in the hypoxic pulmonary artery in either the presence or absence of carbachol. Furthermore, eNOS Ser(1177) phosphorylation in both conditions significantly decreased without affecting Akt phosphorylation in the hypoxic artery. In conclusion, chronic hypoxia impairs endothelial Ca(2+) metabolism and normal coupling between eNOS and caveolin-1 resulted in eNOS inactivity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
44085-92
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12185080-Animals, pubmed-meshheading:12185080-Anoxia, pubmed-meshheading:12185080-Blotting, Western, pubmed-meshheading:12185080-Body Weight, pubmed-meshheading:12185080-Calcium, pubmed-meshheading:12185080-Carbachol, pubmed-meshheading:12185080-Cell Membrane, pubmed-meshheading:12185080-Cyclic GMP, pubmed-meshheading:12185080-Electrophoresis, Polyacrylamide Gel, pubmed-meshheading:12185080-Endothelium, Vascular, pubmed-meshheading:12185080-Golgi Apparatus, pubmed-meshheading:12185080-HSP90 Heat-Shock Proteins, pubmed-meshheading:12185080-Hypertension, Pulmonary, pubmed-meshheading:12185080-Microscopy, Fluorescence, pubmed-meshheading:12185080-Muscle Contraction, pubmed-meshheading:12185080-Nitric Oxide, pubmed-meshheading:12185080-Nitric Oxide Synthase, pubmed-meshheading:12185080-Nitric Oxide Synthase Type III, pubmed-meshheading:12185080-Organ Size, pubmed-meshheading:12185080-Phosphorylation, pubmed-meshheading:12185080-Precipitin Tests, pubmed-meshheading:12185080-Pulmonary Artery, pubmed-meshheading:12185080-Rats, pubmed-meshheading:12185080-Rats, Sprague-Dawley, pubmed-meshheading:12185080-Serine, pubmed-meshheading:12185080-Time Factors
pubmed:year
2002
pubmed:articleTitle
Decreased endothelial nitric-oxide synthase (eNOS) activity resulting from abnormal interaction between eNOS and its regulatory proteins in hypoxia-induced pulmonary hypertension.
pubmed:affiliation
Department of Veterinary Pharmacology, Graduate School of Agriculture and Life Sciences, University of Tokyo, Bunkyo-ku, Japan. murata@jvm2.a.u-tokyo.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't