PMID- 15965081
OWN - NLM
STAT- MEDLINE
DCOM- 20060911
LR  - 20131121
IS  - 0077-8923 (Print)
IS  - 0077-8923 (Linking)
VI  - 1042
DP  - 2005 May
TI  - Pravastatin attenuates ceramide-induced cytotoxicity in mouse cerebral 
      endothelial cells with HIF-1 activation and VEGF upregulation.
PG  - 357-64
AB  - Ceramide is a pro-apoptotic lipid messenger that induces oxidative stress and may 
      mediate apoptosis in cerebral endothelial cells (CECs) induced by 
      TNF-alpha/cycloheximide, lipopolysaccharide, oxidized LDL, IL-1, and amyloid 
      peptide. Exposure of CECs to C2 ceramide for 12 h caused cell death in a 
      concentration-dependent manner, with a LC50 of 30 microM. Statins are inhibitors 
      of 3-hydroxyl-3-methyl coenzyme A reductase which is the rate-limiting enzyme for 
      cholesterol biosynthesis. Pretreatment with pravastatin at 20 microM for 16 h 
      substantially attenuated ceramide cytotoxicity in mouse CECs. Increases in 
      vascular endothelial growth factor (VEGF) expression were detected within 1-3 h 
      after pravastatin treatment. This pravastatin action was accompanied by the 
      activation of hypoxia-inducible factor-1 (HIF-1), a transcription factor known to 
      activate VEGF expression. These results raise the possibility that pravastatin 
      may protect CECs against ceramide-induced death via the HIF-VEGF cascade.
FAU - Chen, Shang-Der
AU  - Chen SD
AD  - Department of Neurology, Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
FAU - Hu, Chaur-Jong
AU  - Hu CJ
FAU - Yang, Ding-I
AU  - Yang DI
FAU - Nassief, Abdullah
AU  - Nassief A
FAU - Chen, Hong
AU  - Chen H
FAU - Yin, Kejie
AU  - Yin K
FAU - Xu, Jan
AU  - Xu J
FAU - Hsu, Chung Y
AU  - Hsu CY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Ann N Y Acad Sci
JT  - Annals of the New York Academy of Sciences
JID - 7506858
RN  - 0 (Ceramides)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (RNA, Messenger)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9007-49-2 (DNA)
RN  - KXO2KT9N0G (Pravastatin)
SB  - IM
MH  - Animals
MH  - Brain/*drug effects/metabolism
MH  - Cell Survival/drug effects
MH  - Cells, Cultured
MH  - Ceramides/*toxicity
MH  - DNA/metabolism
MH  - Endothelial Cells/*drug effects/*metabolism
MH  - Hypoxia-Inducible Factor 1/*metabolism
MH  - Mice
MH  - Pravastatin/*pharmacology
MH  - RNA, Messenger/genetics
MH  - Up-Regulation/drug effects
MH  - Vascular Endothelial Growth Factor A/genetics/*metabolism
EDAT- 2005/06/21 09:00
MHDA- 2006/09/12 09:00
CRDT- 2005/06/21 09:00
PHST- 2005/06/21 09:00 [pubmed]
PHST- 2006/09/12 09:00 [medline]
PHST- 2005/06/21 09:00 [entrez]
AID - 1042/1/357 [pii]
AID - 10.1196/annals.1338.033 [doi]
PST - ppublish
SO  - Ann N Y Acad Sci. 2005 May;1042:357-64. doi: 10.1196/annals.1338.033.