PMID- 19374868
OWN - NLM
STAT- MEDLINE
DCOM- 20090901
LR  - 20131121
IS  - 1879-0712 (Electronic)
IS  - 0014-2999 (Linking)
VI  - 606
IP  - 1-3
DP  - 2009 Mar 15
TI  - The calcium channel blocker cilnidipine selectively suppresses hypoxia-inducible 
      factor 1 activity in vascular cells.
PG  - 130-6
LID - 10.1016/j.ejphar.2009.01.012 [doi]
AB  - 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-1alpha 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.
FAU - Oda, Seiko
AU  - Oda S
AD  - Department of Anesthesia, Kyoto University Hospital, Kyoto, Japan.
FAU - Oda, Tomoyuki
AU  - Oda T
FAU - Takabuchi, Satoshi
AU  - Takabuchi S
FAU - Nishi, Kenichiro
AU  - Nishi K
FAU - Wakamatsu, Takuhiko
AU  - Wakamatsu T
FAU - Tanaka, Tomoharu
AU  - Tanaka T
FAU - Adachi, Takehiko
AU  - Adachi T
FAU - Fukuda, Kazuhiko
AU  - Fukuda K
FAU - Nohara, Ryuji
AU  - Nohara R
FAU - Hirota, Kiichi
AU  - Hirota K
LA  - eng
PT  - Journal Article
DEP - 20090121
PL  - Netherlands
TA  - Eur J Pharmacol
JT  - European journal of pharmacology
JID - 1254354
RN  - 0 (Calcium Channel Blockers)
RN  - 0 (Dihydropyridines)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 97T5AZ1JIP (cilnidipine)
RN  - S88TT14065 (Oxygen)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Calcium/metabolism
MH  - Calcium Channel Blockers/*pharmacology
MH  - Cell Line, Tumor
MH  - Dihydropyridines/*pharmacology
MH  - Gene Expression Regulation/drug effects
MH  - Humans
MH  - Hypoxia-Inducible Factor 1/*antagonists & inhibitors/*metabolism
MH  - Intracellular Space/drug effects/metabolism
MH  - Oxygen/metabolism
MH  - Stress, Physiological/drug effects
EDAT- 2009/04/21 09:00
MHDA- 2009/09/02 06:00
CRDT- 2009/04/21 09:00
PHST- 2008/08/19 00:00 [received]
PHST- 2008/12/17 00:00 [revised]
PHST- 2009/01/09 00:00 [accepted]
PHST- 2009/04/21 09:00 [entrez]
PHST- 2009/04/21 09:00 [pubmed]
PHST- 2009/09/02 06:00 [medline]
AID - S0014-2999(09)00063-6 [pii]
AID - 10.1016/j.ejphar.2009.01.012 [doi]
PST - ppublish
SO  - Eur J Pharmacol. 2009 Mar 15;606(1-3):130-6. doi: 10.1016/j.ejphar.2009.01.012. 
      Epub 2009 Jan 21.