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. Journal of Molecular and Cellular Cardiology. London: Academic Press Ltd - Elsevier Science, roč. 68, March 2014, s. 89-97. ISSN 0022-2828. doi:10.1016/j.yjmcc.2014.01.006. 2014.
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Základní údaje
Originální název BDNF secretion by human pulmonary artery endothelial cells in response to hypoxia
Název česky Sekrece BDNF lidskými endotelovými buňkami plicní artérie jako reakce na hypoxii
Autoři HELÁN, Martin (203 Česká republika, garant, domácí), Bharathi ARAVAMUDAN (840 Spojené státy), William R. HARTMAN (840 Spojené státy), Michael A. THOMPSON (840 Spojené státy), Bruce D. JOHNSON (840 Spojené státy), Christina M. PABELICK (840 Spojené státy) a Y.S. PRAKASH (840 Spojené státy).
Vydání Journal of Molecular and Cellular Cardiology, London, Academic Press Ltd - Elsevier Science, 2014, 0022-2828.
Další údaje
Originální jazyk angličtina
Typ výsledku Článek v odborném periodiku
Obor 30201 Cardiac and Cardiovascular systems
Stát vydavatele Spojené státy
Utajení není předmětem státního či obchodního tajemství
WWW Full text
Impakt faktor Impact factor: 4.655
Kód RIV RIV/00216224:14110/14:00077285
Organizační jednotka Lékařská fakulta
Doi http://dx.doi.org/10.1016/j.yjmcc.2014.01.006
UT WoS 000334653200011
Klíčová slova anglicky Neurotrophin; Tropomyosin related kinase; Nitric oxide; Hypoxia inducible factor 1; iNOS; eNOS
Štítky EL OK
Příznaky Mezinárodní význam, Recenzováno
Změnil Změnila: Soňa Böhmová, učo 232884. Změněno: 27. 1. 2015 17:00.
Anotace
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.
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