PMID- 24612679
OWN - NLM
STAT- MEDLINE
DCOM- 20150109
LR  - 20180816
IS  - 1748-1716 (Electronic)
IS  - 1748-1708 (Linking)
VI  - 211
IP  - 2
DP  - 2014 Jun
TI  - Brain-derived neurotrophic factor promotes angiogenic tube formation through 
      generation of oxidative stress in human vascular endothelial cells.
PG  - 385-94
LID - 10.1111/apha.12249 [doi]
AB  - AIM: Brain-derived neurotrophic factor (BDNF), a major type of neurotrophins, 
      plays a role in the regulation of synaptic function. Recent studies suggest that 
      BDNF promotes angiogenesis through its specific receptor, tropomyosin-related 
      kinase B (TrkB). However, the detailed mechanisms for this still remain to be 
      determined. Reactive oxygen species (ROS) generation contributes to the 
      regulation of angiogenesis. Thus, we investigated the mechanisms by which BDNF 
      regulates angiogenesis with focusing on ROS in cultured human vascular 
      endothelial cells (ECs). METHODS AND RESULTS: In human umbilical vein ECs, BDNF 
      increased ROS generation as measured fluorometrically using 2' 
      7'-dichlorofluorescein diacetate as well as NADPH oxidase (NOX) activity as 
      measured by lucigenin assay. BDNF-induced ROS generation and NOX activity were 
      inhibited by K252a, a TrkB receptor inhibitor. BDNF induced phosphorylation of 
      p47 phox, a regulatory component of NOX, which was inhibited by K252a as measured 
      by Western blotting. BDNF increased angiogenic tube formation in ECs, which was 
      completely inhibited by K252a or gp91ds-tat, a NOX inhibitor. BDNF caused Akt 
      phosphorylation in ECs, which was inhibited by K252a or gp91ds-tat. CONCLUSION: 
      The present results for the first time demonstrate that BDNF induces NOX-derived 
      ROS generation through activation of p47 phox in a TrkB receptor-dependent 
      manner, which leads to the promotion of angiogenic tube formation possibly via 
      Akt activation.
CI  - (c) 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.
FAU - Usui, T
AU  - Usui T
AD  - Laboratory of Veterinary Pharmacology, School of Veterinary Medicine, Kitasato 
      University, Towada, Aomori, Japan.
FAU - Naruo, A
AU  - Naruo A
FAU - Okada, M
AU  - Okada M
FAU - Hayabe, Y
AU  - Hayabe Y
FAU - Yamawaki, H
AU  - Yamawaki H
LA  - eng
PT  - Journal Article
DEP - 20140310
PL  - England
TA  - Acta Physiol (Oxf)
JT  - Acta physiologica (Oxford, England)
JID - 101262545
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (RNA, Small Interfering)
RN  - 0 (p37 protein, human)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 1.6.3.- (NADPH Oxidases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
SB  - IM
CIN - Acta Physiol (Oxf). 2014 Jun;211(2):268-70. PMID: 24720532
MH  - Adaptor Proteins, Signal Transducing/*metabolism
MH  - Blotting, Western
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Cells, Cultured
MH  - Endothelial Cells/*metabolism
MH  - Humans
MH  - NADPH Oxidases/metabolism
MH  - Neovascularization, Physiologic/*physiology
MH  - Oxidative Stress/*physiology
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - RNA, Small Interfering
MH  - Receptor, trkB/*metabolism
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Transfection
OTO - NOTNLM
OT  - NADPH oxidase
OT  - angiogenesis
OT  - reactive oxygen species
OT  - vascular endothelial cell
EDAT- 2014/03/13 06:00
MHDA- 2015/01/13 06:00
CRDT- 2014/03/12 06:00
PHST- 2013/10/24 00:00 [received]
PHST- 2013/12/03 00:00 [revised]
PHST- 2014/01/13 00:00 [revised]
PHST- 2014/01/30 00:00 [accepted]
PHST- 2014/03/12 06:00 [entrez]
PHST- 2014/03/13 06:00 [pubmed]
PHST- 2015/01/13 06:00 [medline]
AID - 10.1111/apha.12249 [doi]
PST - ppublish
SO  - Acta Physiol (Oxf). 2014 Jun;211(2):385-94. doi: 10.1111/apha.12249. Epub 2014 
      Mar 10.