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Cyclic AMP Phosphodiesterase 4D4 Expression in Lung Endothelium is a Determinant of Cell Phenotype
Author(s) -
Creighton Judy,
Zhu Bing,
Alexeyev Mikhail,
Stevens Troy
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a1433-a
Subject(s) - thapsigargin , endothelial stem cell , phosphodiesterase , endothelium , rolipram , microbiology and biotechnology , biology , cell culture , chemistry , immunology , endocrinology , in vitro , enzyme , endoplasmic reticulum , biochemistry , genetics
Endothelial cells that line pulmonary artery and capillary (microvascular) segments are phenotypically distinct. Although the molecular mechanisms responsible for this endothelial heterogeneity are poorly understood, these cells differ in cAMP signaling. We have previously shown that pulmonary microvascular endothelial cells (PMVECs) express phosphodiesterase 4D4 (PDE 4D4) that is not expressed by pulmonary artery endothelial cells (PAECs). Thus, we sought to determine the contribution of PDE 4D4 expression to endothelial phenotype by utilizing a retroviral approach to stably express PDE 4D4 in PAECs (PAEC/D4s). In immunoblot analysis, antibody specific to PDE 4D4 confirmed protein expression. Increased rolipram sensitive PDE 4 activity was detected in PAEC/D4s compared to wild type PAECs and similar to activity observed in PMVECs. PMVECs and PAEC/D4s exhibited greater calcium sensitive adenylyl cyclase (AC) activity compared to PAECs. In resistance studies PAEC/D4 baseline resistance was 40% greater than wild type PAECs, and similar to PMVECs values. Thapsigargin‐induced increase in cytosolic calcium increases permeability and decreases resistance in wild type PAECs, but not in PMVECs or PAEC/D4 cells. Collectively, these studies indicate that PDE 4D4 expression contributes to endothelial phenotype. Supported by HL066299 , HL 060024, and AHA 0415112B.