PMID- 16553631
OWN - NLM
STAT- MEDLINE
DCOM- 20060530
LR  - 20131121
IS  - 0953-816X (Print)
IS  - 0953-816X (Linking)
VI  - 23
IP  - 6
DP  - 2006 Mar
TI  - Secretion of brain-derived neurotrophic factor from brain microvascular 
      endothelial cells.
PG  - 1665-70
AB  - The cerebral microvasculature has recently been identified as a source of factors 
      that can influence the generation and survival of neurons, including 
      brain-derived neurotrophic factor (BDNF). However, relatively little is known 
      about signals that regulate secretion of endothelial cell derived BDNF. To 
      approach this issue the present study examined BDNF secretion from brain 
      endothelial cells in response to reduced oxygen availability (hypoxia), using the 
      mouse brain microvascular endothelial cell line, bEnd.3. We found that exposure 
      of bEnd.3 cells to either sustained or intermittent hypoxia (IH) stimulates BDNF 
      expression and release and that IH is the more potent stimulus. IH-induced BDNF 
      release can be partially inhibited by either N-acetyl-L-cysteine, a scavenger of 
      reactive oxygen species, or by the stable superoxide dismutase mimetic 
      manganese(III)tetrakis1-methyl-4-pyridylporphyrin, indicating that oxyradical 
      formation contributes to enhanced secretion of BDNF. In addition, we found that 
      IH-induced BDNF release requires Ca2+ mobilization from internal stores through 
      ryanodine- and inositol (1,4,5-triphosphate) IP3 receptors and is completely 
      blocked by SKF 96365, a nonselective inhibitor of transient receptor potential 
      (TRP) channels. These data demonstrate that bEnd.3 cells respond to oxidative 
      stress by increasing BDNF secretion and, in addition, highlight TRP channels as 
      potential therapeutic targets for enhancing BDNF availability from the cerebral 
      microvasculature.
FAU - Wang, Hong
AU  - Wang H
AD  - Department of Neurosciences, Case Western Reserve University School of Medicine, 
      10900 Euclid Avenue, Cleveland, Ohio 44106, USA.
FAU - Ward, Nicole
AU  - Ward N
FAU - Boswell, Mark
AU  - Boswell M
FAU - Katz, David M
AU  - Katz DM
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PL  - France
TA  - Eur J Neurosci
JT  - The European journal of neuroscience
JID - 8918110
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Calcium Channels)
RN  - 0 (Free Radical Scavengers)
RN  - 0 (Free Radicals)
RN  - 0 (ITPR1 protein, human)
RN  - 0 (Indicators and Reagents)
RN  - 0 (Inositol 1,4,5-Trisphosphate Receptors)
RN  - 0 (Reactive Oxygen Species)
RN  - 0 (Receptors, Cytoplasmic and Nuclear)
RN  - 0 (Ryanodine Receptor Calcium Release Channel)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/pharmacology
MH  - Calcium Channels/drug effects
MH  - Capillaries/drug effects/metabolism
MH  - Cell Survival/physiology
MH  - Cells, Cultured
MH  - Cerebrovascular Circulation/drug effects/*physiology
MH  - Endothelial Cells/drug effects/*metabolism
MH  - Free Radical Scavengers/pharmacology
MH  - Free Radicals/metabolism
MH  - Humans
MH  - Hypoxia, Brain/metabolism
MH  - Indicators and Reagents
MH  - Inositol 1,4,5-Trisphosphate Receptors
MH  - Oxidative Stress/physiology
MH  - Reactive Oxygen Species/metabolism
MH  - Receptors, Cytoplasmic and Nuclear/drug effects
MH  - Ryanodine Receptor Calcium Release Channel/drug effects
EDAT- 2006/03/24 09:00
MHDA- 2006/05/31 09:00
CRDT- 2006/03/24 09:00
PHST- 2006/03/24 09:00 [pubmed]
PHST- 2006/05/31 09:00 [medline]
PHST- 2006/03/24 09:00 [entrez]
AID - EJN4682 [pii]
AID - 10.1111/j.1460-9568.2006.04682.x [doi]
PST - ppublish
SO  - Eur J Neurosci. 2006 Mar;23(6):1665-70. doi: 10.1111/j.1460-9568.2006.04682.x.