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Secretion of brain‐derived neurotrophic factor from brain microvascular endothelial cells
Author(s) -
Wang Hong,
Ward Nicole,
Boswell Mark,
Katz David M.
Publication year - 2006
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2006.04682.x
Subject(s) - neurotrophic factors , secretion , endocrinology , brain derived neurotrophic factor , medicine , chemistry , endothelial stem cell , microbiology and biotechnology , receptor , neuroprotection , biology , biochemistry , in vitro
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 Ca 2+ mobilization from internal stores through ryanodine‐ and inositol (1,4,5‐triphosphate) IP 3 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.