PMID- 16603689
OWN - NLM
STAT- MEDLINE
DCOM- 20060818
LR  - 20220409
IS  - 0363-6135 (Print)
IS  - 0363-6135 (Linking)
VI  - 291
IP  - 2
DP  - 2006 Aug
TI  - Caveolin-1 and regulation of cellular cholesterol homeostasis.
PG  - H677-86
AB  - Caveolae are 50- to 100-nm cell surface plasma membrane invaginations present in 
      terminally differentiated cells. They are characterized by the presence of 
      caveolin-1, sphingolipids, and cholesterol. Caveolin-1 is thought to play an 
      important role in the regulation of cellular cholesterol homeostasis, a process 
      that needs to be properly controlled to limit and prevent cholesterol 
      accumulation and eventually atherosclerosis. We have recently generated 
      caveolin-1-deficient [Cav-1(-/-)] mice in which caveolae organelles are 
      completely eliminated from all cell types, except cardiac and skeletal muscle. In 
      the present study, we examined the metabolism of cholesterol in wild-type (WT) 
      and Cav-1(-/-) mouse embryonic fibroblasts (MEFs) and mouse peritoneal 
      macrophages (MPMs). We observed that Cav-1(-/-) MEFs are enriched in esterified 
      cholesterol but depleted of free cholesterol compared with their wild-type 
      counterparts. Similarly, Cav-1(-/-) MPMs also contained less free cholesterol and 
      were enriched in esterified cholesterol on cholesterol loading. In agreement with 
      this finding, caveolin-1 deficiency was associated with reduced free cholesterol 
      synthesis but increased acyl-CoA:cholesterol acyl-transferase (ACAT) activity. In 
      wild-type MPMs, we observed that caveolin-1 was markedly upregulated on 
      cholesterol loading. Despite these differences, cellular cholesterol efflux from 
      MEFs and MPMs to HDL was not affected in the Cav-1-deficient cells. Neither 
      ATP-binding cassette transporter G1 (ABCG1)- nor scavenger receptor class B type 
      I (SR-BI)-mediated cholesterol efflux was affected. Cellular cholesterol efflux 
      to apolipoprotein A-I was not significantly reduced in Cav-1(-/-) MPMs compared 
      with wild-type MPMs. However, ABCA1-mediated cholesterol efflux was clearly more 
      sensitive to the inhibitory effects of glyburide in Cav-1(-/-) MPMs versus WT 
      MPMs. Taken together, these findings suggest that caveolin-1 plays an important 
      role in the regulation of intracellular cholesterol homeostasis and can modulate 
      the activity of other proteins that are involved in the regulation of 
      intracellular cholesterol homeostasis.
FAU - Frank, Philippe G
AU  - Frank PG
AD  - Department of Urology, and Albert Einstein Diabetes Research and Training Center, 
      Albert Einstein College of Medicine, Bronx, New York, USA. 
      Philippe.Frank@jefferson.edu
FAU - Cheung, Michelle W-C
AU  - Cheung MW
FAU - Pavlides, Stephanos
AU  - Pavlides S
FAU - Llaverias, Gemma
AU  - Llaverias G
FAU - Park, David S
AU  - Park DS
FAU - Lisanti, Michael P
AU  - Lisanti MP
LA  - eng
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20060407
PL  - United States
TA  - Am J Physiol Heart Circ Physiol
JT  - American journal of physiology. Heart and circulatory physiology
JID - 100901228
RN  - 0 (Apolipoproteins A)
RN  - 0 (Caveolin 1)
RN  - 0 (Cholesterol Esters)
RN  - 0 (Cholesterol, HDL)
RN  - 0 (Cholesterol, LDL)
RN  - 0 (Sterol Regulatory Element Binding Protein 1)
RN  - 97C5T2UQ7J (Cholesterol)
SB  - IM
MH  - Animals
MH  - Apolipoproteins A/metabolism
MH  - Blotting, Western
MH  - Caveolin 1/genetics/*physiology
MH  - Cholesterol/*metabolism
MH  - Cholesterol Esters/metabolism
MH  - Cholesterol, HDL/metabolism
MH  - Cholesterol, LDL/metabolism
MH  - Fibroblasts/metabolism
MH  - Homeostasis/*physiology
MH  - In Vitro Techniques
MH  - Macrophages, Peritoneal/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Mice, Knockout
MH  - Microscopy, Fluorescence
MH  - Sterol Regulatory Element Binding Protein 1/metabolism
EDAT- 2006/04/11 09:00
MHDA- 2006/08/19 09:00
CRDT- 2006/04/11 09:00
PHST- 2006/04/11 09:00 [pubmed]
PHST- 2006/08/19 09:00 [medline]
PHST- 2006/04/11 09:00 [entrez]
AID - 01092.2005 [pii]
AID - 10.1152/ajpheart.01092.2005 [doi]
PST - ppublish
SO  - Am J Physiol Heart Circ Physiol. 2006 Aug;291(2):H677-86. doi: 
      10.1152/ajpheart.01092.2005. Epub 2006 Apr 7.