Fluoxetine Protects against Big Endothelin-1 Induced Anti-Apoptosis by Rescuing Kv1.5 Channels in Human Pulmonary Arterial Smooth Muscle Cells.
10.3349/ymj.2012.53.4.842
- Author:
Feifeng DAI
1
;
Zhifu MAO
;
Jun XIA
;
Shaoping ZHU
;
Zhiyong WU
Author Information
1. Department of Cardiothoracic Surgery, Renmin Hospital of Wuhan University, Wuhan, China. zfmao2007@163.com
- Publication Type:Original Article
- Keywords:
Apoptosis;
Kv1.5;
human pulmonary arterial smooth muscle cells
- MeSH:
Apoptosis/drug effects/genetics;
Blotting, Western;
Cell Proliferation/drug effects;
Cells, Cultured;
Endothelin-1/*pharmacology;
Flow Cytometry;
Fluoxetine/*pharmacology;
Humans;
Kv1.5 Potassium Channel/genetics/*metabolism;
Muscle, Smooth, Vascular/*cytology/drug effects;
Pulmonary Artery/*cytology;
Reverse Transcriptase Polymerase Chain Reaction
- From:Yonsei Medical Journal
2012;53(4):842-848
- CountryRepublic of Korea
- Language:English
-
Abstract:
PURPOSE: 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. MATERIALS AND 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. CONCLUSION: 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+.
