CI- -channel is essential for LDL-induced cell proliferation via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1 in human aortic smooth muscle cells

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Title
CI- -channel is essential for LDL-induced cell proliferation via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1 in human aortic smooth muscle cells
Author(s)
Kyung Sun Heo; S W Ryoo; L Kim; Mi-Young Nam; S T Baek; Hye Mi Lee; Ah-Reum Lee; Song Kyu Park; Young Woo Park; C S Myung; Dong Uk Kim; Kwang Lae Hoe
Bibliographic Citation
Molecules and Cells, vol. 26, no. 5, pp. 468-473
Publication Year
2008
Abstract
Low-density lipoprotein (LDL) induces cell proliferation in human aortic smooth muscle cells (hAoSMCs), which may be involved in atherogenesis and intimal hyperplasia. Recent studies have demonstrated that Cl- channels are related to vessel cell proliferation induced by a variety of stimuli. In this study, we investigated a potential role of Cl- channels in the signaling pathway of LDL effects on hAoSMC proliferation with a focus on the activation of Erk1/2-PI3K/Akt and the subsequent upregulation of Egr-1. Cl- channel blockers, DIDS, but neither NPPB nor Furosemide, completely abolished the LDL-induced DNA synthesis and cell proliferation. Moreover, DIDS, but not NPPB, significantly decreased LDL-stimulated Cl- concentration, as judged by flow cytometry analysis using MQAE as a Cl-detection dye. DIDS pretreatment completely abolished the activation of Erk1/2 and PI3K/Akt in a dose-dependent manner that is the hallmark of LDL activation, as judged by Western blot and proliferation assays. Moreover, pretreatment with DIDS (Cl- channel blockers) but not LY294002 (PI3K inhibitors) completely abolished the LDL-induced upregulation of Egr-1 to the same extent as PD98059 (MEK inhibitors to inhibit Erk), as judged by Western blot and luciferase reporter assays. This is the first report, to our knowledge, that DIDS-sensitive Cl- channels play a key role in the LDL-induced cell proliferation of hAoSMCs via the activation of Erk1/2 and PI3K/Akt and the upregulation of Egr-1.
Keyword
Cl- channelDIDSEgr-1low-density lipoproteinPI3K
ISSN
1016-8478
Publisher
Korea Soc-Assoc-Inst
Type
Article
Appears in Collections:
Division of Biomedical Research > Rare Disease Research Center > 1. Journal Articles
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