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Activation of AKT and endothelial nitric oxide synthase by BMP2 and BMP4 in bovine pulmonary artery endothelial cells
Author(s) -
Bauer Philip Michael,
Oran Max,
Wertz Jeffrey W.
Publication year - 2008
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.22.1_supplement.915.4
Subject(s) - enos , protein kinase b , bmpr2 , bone morphogenetic protein 2 , medicine , nitric oxide , nitric oxide synthase type iii , chemistry , signal transduction , microbiology and biotechnology , endocrinology , bone morphogenetic protein , nitric oxide synthase , cancer research , biology , biochemistry , gene , in vitro
Mutations in the bone morphogenetic protein (BMP) receptor‐2 (BMPR2) are causally linked to familial pulmonary arterial hypertension (PAH). The mechanistic link between loss of BMPR2 signaling and development of PAH, however, remains unclear. Recently it was demonstrated that BMPR2 signaling promotes survival in pulmonary artery endothelial cells (ECs). Activation of the protein kinase AKT and its downstream target endothelial nitric oxide synthase (eNOS) are known to promote EC survival. We hypothesized that treatment of ECs with the BMPR2 ligands, BMP2 or BMP4, would result in activation of AKT and eNOS and result in nitric oxide (NO) release from ECs. Serum starved ECs were treated with vascular endothelial growth factor (VEGF; 50 ng/ml), BMP2 (30 ng/ml) or BMP4 (30 ng/ml) for 0, 5, 15, or 30 min. Western blot analysis revealed that both AKT and eNOS were phosphorylated in response to BMP2 and BMP4 similar to the AKT/eNOS activator VEGF. Likewise BMP2 and BMP4 treatment resulted in increased NO release from ECs as determined by nitrite accumulation in the cell culture medium. These data provide the first evidence that BMP signaling leads activation of this important survival pathway in ECs and represent a possible mechanism by which loss of BMPR2 signaling could lead to the pathogenesis of PAH. This work was supported by seed funds provided by the Department of Surgery, University of Pittsburgh School of Medicine.