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@article{1205789, author = {Helán, Martin and Aravamudan, Bharathi and Hartman, William R. and Thompson, Michael A. and Johnson, Bruce D. and Pabelick, Christina M. and Prakash, Y.S.}, article_location = {London}, article_number = {March 2014}, doi = {http://dx.doi.org/10.1016/j.yjmcc.2014.01.006}, keywords = {Neurotrophin; Tropomyosin related kinase; Nitric oxide; Hypoxia inducible factor 1; iNOS; eNOS}, language = {eng}, issn = {0022-2828}, journal = {Journal of Molecular and Cellular Cardiology}, title = {BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia}, url = {http://www.sciencedirect.com/science/article/pii/S0022282814000169}, volume = {68}, year = {2014} }
TY - JOUR ID - 1205789 AU - Helán, Martin - Aravamudan, Bharathi - Hartman, William R. - Thompson, Michael A. - Johnson, Bruce D. - Pabelick, Christina M. - Prakash, Y.S. PY - 2014 TI - BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia JF - Journal of Molecular and Cellular Cardiology VL - 68 IS - March 2014 SP - 89-97 EP - 89-97 PB - Academic Press Ltd - Elsevier Science SN - 00222828 KW - Neurotrophin KW - Tropomyosin related kinase KW - Nitric oxide KW - Hypoxia inducible factor 1 KW - iNOS KW - eNOS UR - http://www.sciencedirect.com/science/article/pii/S0022282814000169 N2 - Within human pulmonary artery, neurotrophin growth factors [NTs; e.g. brain-derived neurotrophic factor (BDNF)] and their high-affinity receptors (tropomyosin-related kinase; Trk) and low-affinity receptors p75 neurotrophin receptor (p75NTR) have been reported, but their functional role is incompletely understood. We tested the hypothesis that BDNF is produced by human pulmonary artery endothelial cells (PAECs). In the context of hypoxia as a risk factor for pulmonary hypertension, we examined the effect of hypoxia on BDNF secretion and consequent autocrine effects on pulmonary endothelium. Initial ELISA analysis of circulating BDNF in 30 healthy human volunteers showed that 72 h exposure to high altitude (similar to 11,000 ft, alveolar PO2 = 100 mm Hg) results in higher BDNF compared to samples taken at sea level. Separately, in human PAECs exposed for 24 h to normoxia vs. hypoxia (1-3% O-2), ELISA of extracellular media showed increased BDNF levels. Furthermore, quantitative PCR of PAECs showed 3-fold enhancement of BDNF gene transcription with hypoxia. In PAECs, BDNF induced NO production (measured using an NO-sensitive fluorescent dye DAF2-DA) that was significantly higher under hypoxic conditions, an effect also noted with the TrkB agonist 7,8-DHF. Importantly, hypoxia-induced NO was blunted by neutralization of secreted BDNF using the chimeric TrkB-Fc. Both hypoxia and BDNF increased iNOS (but not eNOS) mRNA expression. In accordance, BDNF enhancement of NO in hypoxia was not blunted by 50 nM L-NAME (eNOS inhibition) but substantially lower with 100 mu M L-NAME (eNOS and iNOS inhibition). Hypoxia and BDNF also induced expression of hypoxia inducible factor 1 alpha (HIF-1 alpha), a subunit of the transcription factor HIF-1, and pharmacological inhibition of HIF-1 diminished hypoxia effects on BDNF expression and secretion, and NO production. These results indicate that human PAECs express and secrete BDNF in response to hypoxia via a HIF-1-regulated pathway. ER -
HELÁN, Martin, Bharathi ARAVAMUDAN, William R. HARTMAN, Michael A. THOMPSON, Bruce D. JOHNSON, Christina M. PABELICK a Y.S. PRAKASH. BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia. \textit{Journal of Molecular and Cellular Cardiology}. London: Academic Press Ltd - Elsevier Science, 2014, roč.~68, March 2014, s.~89-97. ISSN~0022-2828. Dostupné z: https://dx.doi.org/10.1016/j.yjmcc.2014.01.006.
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