PMID- 14660607
OWN - NLM
STAT- MEDLINE
DCOM- 20040430
LR  - 20210206
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 279
IP  - 8
DP  - 2004 Feb 20
TI  - Caveolin-1 knockdown by small interfering RNA suppresses responses to the 
      chemokine monocyte chemoattractant protein-1 by human astrocytes.
PG  - 6688-95
AB  - Astrocytes regulate the integrity of the blood-brain barrier and influence 
      inflammatory processes in the central nervous system. The pro-inflammatory 
      chemokine monocyte chemoattractant protein-1 (MCP-1), which is both released by 
      and stimulates astrocytes, is thought to play a crucial role in both these 
      activities. Because astrocytes have been shown to possess caveolae, vesicular 
      structures that participate in intracellular transport and signal transduction 
      events, we reasoned that expression of the major structural protein of these 
      organelles, caveolin-1, might feature critically in the cellular responses to 
      MCP-1. To test this hypothesis, caveolin-1 level was "knocked down" in human 
      astrocyte cultures by using a small interfering RNA approach. This method 
      resulted in efficient (>90% loss) and specific knockdown of caveolin-1 expression 
      while sparring glial fibrillary acidic protein as well as several other proteins 
      involved in endocytosis. Astrocytes suffering caveolin-1 loss showed diminished 
      ability to down-modulate and internalize the MCP-1 receptor (CCR2) in response to 
      exposure to this chemokine and also demonstrated significantly reduced capacity 
      to undergo chemotaxis and calcium flux when MCP-1-stimulated. The results 
      highlight a potentially prominent role for caveolae and/or caveolin-1 in 
      mediating astrocyte responses to MCP-1, a feature that might significantly 
      dictate the progression of inflammatory events at the blood-brain barrier.
FAU - Ge, Shujun
AU  - Ge S
AD  - Blood-Brain Barrier Laboratory, Department of Pharmacology, University of 
      Connecticut Health Center, Farmington, Connecticut 06030, USA.
FAU - Pachter, Joel S
AU  - Pachter JS
LA  - eng
GR  - R01-MH54718/MH/NIMH NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
DEP - 20031205
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (CAV1 protein, human)
RN  - 0 (Caveolin 1)
RN  - 0 (Caveolins)
RN  - 0 (Chemokine CCL2)
RN  - 0 (Culture Media, Serum-Free)
RN  - 0 (Glial Fibrillary Acidic Protein)
RN  - 0 (Protein Synthesis Inhibitors)
RN  - 0 (RNA, Small Interfering)
RN  - 63231-63-0 (RNA)
RN  - 98600C0908 (Cycloheximide)
RN  - SY7Q814VUP (Calcium)
SB  - IM
MH  - Astrocytes/*metabolism
MH  - Binding Sites
MH  - Blood-Brain Barrier
MH  - Blotting, Western
MH  - Calcium/metabolism
MH  - Caveolin 1
MH  - Caveolins/*metabolism
MH  - Cells, Cultured
MH  - Chemokine CCL2/*metabolism
MH  - Chemotaxis
MH  - Culture Media, Serum-Free/pharmacology
MH  - Cycloheximide/pharmacology
MH  - Dose-Response Relationship, Drug
MH  - Down-Regulation
MH  - Endocytosis
MH  - Glial Fibrillary Acidic Protein/metabolism
MH  - Humans
MH  - Immunohistochemistry
MH  - Kinetics
MH  - Phosphorylation
MH  - Protein Binding
MH  - Protein Synthesis Inhibitors/pharmacology
MH  - RNA/metabolism
MH  - RNA, Small Interfering/*metabolism
MH  - Time Factors
MH  - Transcription, Genetic
MH  - Transfection
EDAT- 2003/12/09 05:00
MHDA- 2004/05/01 05:00
CRDT- 2003/12/09 05:00
PHST- 2003/12/09 05:00 [pubmed]
PHST- 2004/05/01 05:00 [medline]
PHST- 2003/12/09 05:00 [entrez]
AID - S0021-9258(18)44625-X [pii]
AID - 10.1074/jbc.M311769200 [doi]
PST - ppublish
SO  - J Biol Chem. 2004 Feb 20;279(8):6688-95. doi: 10.1074/jbc.M311769200. Epub 2003 
      Dec 5.