The calcium channel blocker cilnidipine selectively suppresses hypoxia-inducible factor 1 activity in vascular cells
Calcium ion is one of the most important second messengers of cellular signal transduction including hypoxia-elicited signals. In this study, we investigated the effects of the L-type calcium channel blockers such as nifedipine, efonidipine cilnidipine, diltiazem, and verapamil, on the activity of h...
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| Veröffentlicht in: | European journal of pharmacology 2009-03, Vol.606 (1), p.130-136 |
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| creator | Oda, Seiko Oda, Tomoyuki Takabuchi, Satoshi Nishi, Kenichiro Wakamatsu, Takuhiko Tanaka, Tomoharu Adachi, Takehiko Fukuda, Kazuhiko Nohara, Ryuji Hirota, Kiichi |
| description | Calcium ion is one of the most important second messengers of cellular signal transduction including hypoxia-elicited signals. In this study, we investigated the effects of the L-type calcium channel blockers such as nifedipine, efonidipine cilnidipine, diltiazem, and verapamil, on the activity of hypoxia-inducible factor-1 (HIF-1), a key transcription factor in control of hypoxia-induced gene expression. Using the lung carcinoma cell line A549 cells, human aortic smooth muscle cells, and human umbilical vein endothelial cells, we demonstrated that cilnidipine exclusively suppressed HIF-1 activity and the expressions of downstream genes in a cell-type specific manner. We also demonstrated that cilnidipine blocked the synthesis of the HIF-1α protein not by affecting activity of the intracellular hypoxia-sensing element prolyl hydroxylases but inhibiting activity of Akt and mitogen-activated protein kinase and that the inhibition is not dependent on the effect on calcium homeostasis. |
| doi_str_mv | 10.1016/j.ejphar.2009.01.012 |
| format | Article |
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In this study, we investigated the effects of the L-type calcium channel blockers such as nifedipine, efonidipine cilnidipine, diltiazem, and verapamil, on the activity of hypoxia-inducible factor-1 (HIF-1), a key transcription factor in control of hypoxia-induced gene expression. Using the lung carcinoma cell line A549 cells, human aortic smooth muscle cells, and human umbilical vein endothelial cells, we demonstrated that cilnidipine exclusively suppressed HIF-1 activity and the expressions of downstream genes in a cell-type specific manner. We also demonstrated that cilnidipine blocked the synthesis of the HIF-1α protein not by affecting activity of the intracellular hypoxia-sensing element prolyl hydroxylases but inhibiting activity of Akt and mitogen-activated protein kinase and that the inhibition is not dependent on the effect on calcium homeostasis.</description><identifier>ISSN: 0014-2999</identifier><identifier>EISSN: 1879-0712</identifier><identifier>DOI: 10.1016/j.ejphar.2009.01.012</identifier><identifier>PMID: 19374868</identifier><identifier>CODEN: EJPHAZ</identifier><language>eng</language><publisher>Amsterdam: Elsevier B.V</publisher><subject>Biological and medical sciences ; Calcium - metabolism ; Calcium channel blocker ; Calcium Channel Blockers - pharmacology ; Cell Line, Tumor ; Dihydropyridines - pharmacology ; Gene Expression Regulation - drug effects ; Humans ; Hypoxia ; Hypoxia-inducible factor 1 (HIF-1) ; Hypoxia-Inducible Factor 1 - antagonists & inhibitors ; Hypoxia-Inducible Factor 1 - metabolism ; Intracellular Space - drug effects ; Intracellular Space - metabolism ; Medical sciences ; Oxygen - metabolism ; Pharmacology. Drug treatments ; Smooth muscle cell ; Stress, Physiological - drug effects ; Translation ; Vascular endothelial cell</subject><ispartof>European journal of pharmacology, 2009-03, Vol.606 (1), p.130-136</ispartof><rights>2009 Elsevier B.V.</rights><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c456t-c3d73847a86c0a43fe6fc23a0227a21195ad426ceaf2dd9048d1920b727e938d3</citedby><cites>FETCH-LOGICAL-c456t-c3d73847a86c0a43fe6fc23a0227a21195ad426ceaf2dd9048d1920b727e938d3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.ejphar.2009.01.012$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3550,27924,27925,45995</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=21295205$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/19374868$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Oda, Seiko</creatorcontrib><creatorcontrib>Oda, Tomoyuki</creatorcontrib><creatorcontrib>Takabuchi, Satoshi</creatorcontrib><creatorcontrib>Nishi, Kenichiro</creatorcontrib><creatorcontrib>Wakamatsu, Takuhiko</creatorcontrib><creatorcontrib>Tanaka, Tomoharu</creatorcontrib><creatorcontrib>Adachi, Takehiko</creatorcontrib><creatorcontrib>Fukuda, Kazuhiko</creatorcontrib><creatorcontrib>Nohara, Ryuji</creatorcontrib><creatorcontrib>Hirota, Kiichi</creatorcontrib><title>The calcium channel blocker cilnidipine selectively suppresses hypoxia-inducible factor 1 activity in vascular cells</title><title>European journal of pharmacology</title><addtitle>Eur J Pharmacol</addtitle><description>Calcium ion is one of the most important second messengers of cellular signal transduction including hypoxia-elicited signals. In this study, we investigated the effects of the L-type calcium channel blockers such as nifedipine, efonidipine cilnidipine, diltiazem, and verapamil, on the activity of hypoxia-inducible factor-1 (HIF-1), a key transcription factor in control of hypoxia-induced gene expression. Using the lung carcinoma cell line A549 cells, human aortic smooth muscle cells, and human umbilical vein endothelial cells, we demonstrated that cilnidipine exclusively suppressed HIF-1 activity and the expressions of downstream genes in a cell-type specific manner. 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| subjects | Biological and medical sciences Calcium - metabolism Calcium channel blocker Calcium Channel Blockers - pharmacology Cell Line, Tumor Dihydropyridines - pharmacology Gene Expression Regulation - drug effects Humans Hypoxia Hypoxia-inducible factor 1 (HIF-1) Hypoxia-Inducible Factor 1 - antagonists & inhibitors Hypoxia-Inducible Factor 1 - metabolism Intracellular Space - drug effects Intracellular Space - metabolism Medical sciences Oxygen - metabolism Pharmacology. Drug treatments Smooth muscle cell Stress, Physiological - drug effects Translation Vascular endothelial cell |
| title | The calcium channel blocker cilnidipine selectively suppresses hypoxia-inducible factor 1 activity in vascular cells |
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