Premium
Secretion of brain‐derived neurotrophic factor from PC12 cells in response to oxidative stress requires autocrine dopamine signaling
Author(s) -
Wang Hong,
Yuan Guoxiang,
Prabhakar Nanduri R.,
Boswell Mark,
Katz David M.
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2005.03572.x
Subject(s) - autocrine signalling , oxidative stress , neurotrophic factors , dopamine , endocrinology , medicine , brain derived neurotrophic factor , dopaminergic , secretion , biology , chemistry , microbiology and biotechnology , receptor
Expression of brain‐derived neurotrophic factor (BDNF) is sensitive to changes in oxygen availability, suggesting that BDNF may be involved in adaptive responses to oxidative stress. However, it is unknown whether or not oxidative stress actually increases availability of BDNF by stimulating BDNF secretion. To approach this issue we examined BDNF release from PC12 cells, a well‐established model of neurosecretion, in response to hypoxic stimuli. BDNF secretion from neuronally differentiated PC12 cells was strongly stimulated by exposure to intermittent hypoxia (IH). This response was inhibited by N ‐acetyl‐ l ‐cysteine, a potent scavenger of reactive oxygen species (ROS) and mimicked by exogenous ROS. IH‐induced BDNF release requires activation of tetrodotoxin sensitive Na + channels and Ca 2+ influx through N‐ and L‐type channels, as well as mobilization of internal Ca 2+ stores. These results demonstrate that oxidative stress can stimulate BDNF release and that underlying mechanisms are similar to those previously described for activity‐dependent BDNF secretion from neurons. Surprisingly, we also found that IH‐induced secretion of BDNF was blocked by dopamine D 2 receptor antagonists or by inhibition of dopamine synthesis with α‐methyl‐ p ‐tyrosine. These data indicate that oxidative stress can stimulate BDNF release through an autocrine or paracrine loop that requires dopamine receptor activation.