PMID- 15238223
OWN - NLM
STAT- MEDLINE
DCOM- 20040810
LR  - 20220317
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1683
IP  - 1-3
DP  - 2004 Jul 5
TI  - Human ATP-binding cassette transporter-2 (ABCA2) positively regulates low-density 
      lipoprotein receptor expression and negatively regulates cholesterol 
      esterification in Chinese hamster ovary cells.
PG  - 89-100
AB  - We present evidence that the ATP binding-cassette transporter-2 (ABCA2) is a 
      sterol-responsive gene that has a role in the trafficking of low-density 
      lipoprotein-derived free cholesterol (LDL-FC). In HepG2 cells ABCA2 was 
      coordinately expressed with other sterol-responsive genes. Stable constitutive 
      expression of ABCA2 in Chinese hamster ovary cells (CHOA2) was accompanied by an 
      increase the expression of the low-density lipoprotein receptor (LDLR) and other 
      genes involved in the regulation of cholesterol homeostasis. LDLR mRNA was 
      elevated greater than ninefold and 3-hydroxy-3-methylglutaryl CoA synthase 
      (HMGCoA S) expression was elevated sevenfold in CHOA2 cells. The increase in LDLR 
      expression was regulated at the level of transcription; however, culture of CHO 
      and CHOA2 cells in medium containing lipoprotein-deficient serum (LPDS) results 
      in similar levels of LDLR promoter expression. No differences were measured in 
      the dose-dependent uptake of fluorescently labeled 
      1,1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchorate-LDL (DiI-LDL) 
      between CHO and CHOA2 cells cultured in medium containing LPDS. Ultraviolet 
      microscopy revealed a similar distribution of the DiI-LDL label in cytoplasmic 
      vesicles. We measured an LDL dose-dependent reduction in esterification of LDL-FC 
      in intact CHOA2 cells cultured in medium containing LPDS, however, no significant 
      difference was measured in acylcoenzyme A:cholesterol acyltransferase (ACAT) 
      activity in cell-free extracts of CHO and CHOA2 cells. CHO cells or CHOA2 cells 
      treated with the hydrophobic amine, U18666A, showed similar filipin staining of 
      unesterified cholesterol in cytoplasmic vesicles. Addition of progesterone or 
      U18666A to CHO cells elevated ABCA2 expression. Finally, we found that ABCA2 
      expression was elevated in Niemann-Pick type C1 (NPC1) fibroblasts and in 
      Familial Hypercholesterolemia (FHC) fibroblasts.
FAU - Davis, Warren Jr
AU  - Davis W Jr
AD  - Department of Pharmacology, Fox Chase Cancer Center, Philadelphia, PA 19111, USA.
FAU - Boyd, Jonathan T
AU  - Boyd JT
FAU - Ile, Kristina E
AU  - Ile KE
FAU - Tew, Kenneth D
AU  - Tew KD
LA  - eng
GR  - CA06927/CA/NCI NIH HHS/United States
GR  - CA83778/CA/NCI NIH HHS/United States
GR  - RR05539/RR/NCRR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (ABCA2 protein, human)
RN  - 0 (ATP-Binding Cassette Transporters)
RN  - 0 (Androstenes)
RN  - 0 (RNA, Messenger)
RN  - 0 (Receptors, LDL)
RN  - 3039-71-2 (3-beta-(2-(diethylamino)ethoxy)androst-5-en-17-one)
RN  - 4G7DS2Q64Y (Progesterone)
RN  - 97C5T2UQ7J (Cholesterol)
RN  - EC 2.3.3.10 (Hydroxymethylglutaryl-CoA Synthase)
SB  - IM
MH  - ATP-Binding Cassette Transporters/*pharmacology
MH  - Androstenes/pharmacology
MH  - Animals
MH  - CHO Cells
MH  - Carcinoma, Hepatocellular/*metabolism/pathology
MH  - Cholesterol/*metabolism
MH  - Cricetinae
MH  - Down-Regulation
MH  - Esterification
MH  - Fibroblasts/*metabolism/pathology
MH  - Humans
MH  - Hydroxymethylglutaryl-CoA Synthase/metabolism
MH  - Hypercholesterolemia/metabolism/pathology
MH  - Liver Neoplasms/metabolism/pathology
MH  - Niemann-Pick Diseases/metabolism/pathology
MH  - Progesterone/pharmacology
MH  - RNA, Messenger/genetics/metabolism
MH  - Receptors, LDL/genetics/*metabolism
MH  - Tumor Cells, Cultured
MH  - Up-Regulation
EDAT- 2004/07/09 05:00
MHDA- 2004/08/11 05:00
CRDT- 2004/07/09 05:00
PHST- 2004/02/04 00:00 [received]
PHST- 2004/04/14 00:00 [revised]
PHST- 2004/04/30 00:00 [accepted]
PHST- 2004/07/09 05:00 [pubmed]
PHST- 2004/08/11 05:00 [medline]
PHST- 2004/07/09 05:00 [entrez]
AID - S1388198104000678 [pii]
AID - 10.1016/j.bbalip.2004.04.009 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2004 Jul 5;1683(1-3):89-100. doi: 
      10.1016/j.bbalip.2004.04.009.