Cl- -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
SCIE
SCOPUS
KCI
- Title
- Cl- -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
- Authors
- Heo, KS; Ryoo, SW; Kim, L; Nam, M; Baek, ST; Lee, H; Lee, AR; Park, SK; Park, Y; Myung, CS; Kim, DU; Hoe, KL
- Date Issued
- 2008-11-30
- Publisher
- Korean Society for Molecular and Cellular Biology
- 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 CI- channels are related to vessel cell proliferation induced by a variety of stimuli. In this study, we investigated a potential role of CI(-)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. CI- 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 CI- concentration, as judged by flow cytometry analysis using MQAE as a CI--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 (CI- 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.
- URI
- https://oasis.postech.ac.kr/handle/2014.oak/37064
- ISSN
- 1016-8478
- Article Type
- Article
- Citation
- Molecules and cells, vol. 26, no. 5, page. 468 - 473, 2008-11-30
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