Fluoxetine protects against big endothelin-1 induced anti-apoptosis by rescuing Kv1.5 channels in human pulmonary arterial smooth muscle cells.
OBJECTIVE
Pulmonary Kv channels are thought to play a crucial role in the regulation of cell proliferation and apoptosis. Previous studies have shown that fluoxetine upregulated the expression of Kv1.5 and prevented pulmonary arterial hypertension in monocrotaline-induced or hypoxia-induced rats and mice. The current study was designed to test how fluoxetine regulates Kv1.5 channels, subsequently promoting apoptosis in human PASMCs cultured in vitro.


METHODS
Human PASMCs were incubated with low-serum DMEM, ET-1, and fluoxetine with and without ET-1 separately for 72 h. Then the proliferation, apoptosis, and expression of TRPC1 and Kv1.5 were detected.


RESULTS
In the ET-1 induced group, the upregulation of TRPC1 and down regulation of Kv1.5 enhanced proliferation and anti-apoptosis, which was reversed when treated with fluoxetine. The decreased expression of TRPC1 increased the expression of Kv1.5, subsequently inhibiting proliferation while promoting apoptosis.


CONCLUSIONS
The results from the present study suggested that fluoxetine protects against big endothelin-1 induced anti-apoptosis and rescues Kv1.5 channels in human pulmonary arterial smooth muscle cells, potentially by decreasing intracellular concentrations of Ca²⁺.
Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China.
FeiFeng
F
Dai
ZhiFu
Z
Mao
Jun
J
Xia
ShaoPing
S
Zhu
ZhiYong
Z
Wu
D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D019332:Endothelin-1 / Q000494:pharmacology*; D005434:Flow Cytometry; D005473:Fluoxetine / Q000494:pharmacology*; D006801:Humans; D051666:Kv1.5 Potassium Channel / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology* / Q000187:drug effects; D011651:Pulmonary Artery / Q000166:cytology*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D019332:Endothelin-1; C496981:KCNA5 protein, human; D051666:Kv1.5 Potassium Channel; D005473:Fluoxetine