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Dopamine release in PC12 cells is mediated by Ca 2+ ‐dependent production of ceramide via sphingomyelin pathway
Author(s) -
Jeon Hyung Jun,
Lee Dong Hoon,
Kang Mi Sun,
Lee MiOck,
Jung Kwang Mook,
Jung Sung Yun,
Kim Dae Kyong
Publication year - 2005
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.1471-4159.2005.03403.x
Subject(s) - ceramide , sphingomyelin , egta , dopamine , ionophore , biophysics , chemistry , biochemistry , second messenger system , calcium , microbiology and biotechnology , membrane , biology , intracellular , endocrinology , apoptosis , organic chemistry
A presynaptic membrane disturbance is an essential process for the release of various neurotransmitters. Ceramide, which is a tumor suppressive lipid, has been shown to act as a channel‐forming molecule and serve as a precursor of ceramide‐1‐phosphate, which can disturb the cellular membrane. This study found that while permeable ceramide increases the rate of dopamine release in the presence of a Ca 2+ ‐ionophore, A23187, permeable ceramide‐1‐phosphate provoked its release even without the ionophore. The treatment of PC12 cells with the ionophore at concentrations < 2 µ m produced ceramide via the sphingomyelin (SM) pathway with a concomitant release of dopamine, and no cell damage was observed. The addition of a Ca 2+ chelator, EGTA, to the medium inhibited the increase in the release of both the ceramide and dopamine. This suggests that ceramide might be produced by Ca 2+ and is implicated in the membrane disturbance associated with the release of dopamine as a result of its conversion to ceramide‐1‐phosphate. Consistent with these results, this study detected a membrane‐associated and neutral pH optimum sphingomyelinase (SMase) whose activity was increased by Ca 2+ . Together, these results demonstrate that ceramide can be produced via the activation of a neutral form of SMase through Ca 2+ , and is involved in the dopamine release in concert with Ca 2+ .