PMID- 10514484
OWN - NLM
STAT- MEDLINE
DCOM- 19991119
LR  - 20190508
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 42
DP  - 1999 Oct 15
TI  - Unique lipoproteins secreted by primary astrocytes from wild type, apoE (-/-),
      and human apoE transgenic mice.
PG  - 30001-7
AB  - Composition of central nervous system lipoproteins affects the metabolism of
      lipoprotein constituents within the brain. The epsilon4 allele of apolipoprotein 
      E (apoE) is a risk factor for Alzheimer's disease via an unknown mechanism(s). As
      glia are the primary central nervous system cell type that synthesize apoE, we
      characterized lipoproteins secreted by astrocytes from wild type (WT), apoE
      (-/-), and apoE transgenic mice expressing human apoE3 or apoE4 in a mouse apoE
      (-/-) background. Nondenaturing size exclusion chromatography demonstrates that
      WT, apoE3, and apoE4 astrocytes secrete particles the size of plasma high density
      lipoprotein (HDL) composed of phospholipid, free cholesterol, and protein,
      primarily apoE and apoJ. However, the lipid:apoE ratio of particles containing
      human apoE is significantly lower than WT. ApoE localizes across HDL-like
      particle sizes. ApoJ localizes to the smallest HDL-like particles. ApoE (-/-)
      astrocytes secrete little phospholipid or free cholesterol despite comparable
      apoJ expression, suggesting that apoE is required for normal secretion of
      astrocyte lipoproteins. Further, particles were not detected in apoE (-/-)
      samples by electron microscopy. Nondenaturing immunoprecipitation experiments
      indicate that apoE and apoJ reside predominantly on distinct particles. These
      studies suggest that apoE expression influences the unique structure of astrocyte
      lipoproteins, a process further modified by apoE species.
FAU - Fagan, A M
AU  - Fagan AM
AD  - Center for the Study of Nervous System Injury, Washington University School of
      Medicine, St. Louis, Missouri 63110, USA. fagana@neuro.wustl.edu
FAU - Holtzman, D M
AU  - Holtzman DM
FAU - Munson, G
AU  - Munson G
FAU - Mathur, T
AU  - Mathur T
FAU - Schneider, D
AU  - Schneider D
FAU - Chang, L K
AU  - Chang LK
FAU - Getz, G S
AU  - Getz GS
FAU - Reardon, C A
AU  - Reardon CA
FAU - Lukens, J
AU  - Lukens J
FAU - Shah, J A
AU  - Shah JA
FAU - LaDu, M J
AU  - LaDu MJ
LA  - eng
GR  - R01 AG013956/AG/NIA NIH HHS/United States
GR  - AG00861-01/AG/NIA NIH HHS/United States
GR  - AG05681-16/AG/NIA NIH HHS/United States
GR  - AG13956/AG/NIA 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.
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Apolipoproteins E)
RN  - 0 (Lipoproteins)
SB  - IM
MH  - Animals
MH  - Apolipoproteins E/*genetics
MH  - Astrocytes/*metabolism/ultrastructure
MH  - Cells, Cultured
MH  - Chromatography, Gel
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Humans
MH  - Lipoproteins/isolation & purification/*metabolism/ultrastructure
MH  - Mice
MH  - Mice, Transgenic
MH  - Microscopy, Electron
EDAT- 1999/10/09 00:00
MHDA- 1999/10/09 00:01
CRDT- 1999/10/09 00:00
PHST- 1999/10/09 00:00 [pubmed]
PHST- 1999/10/09 00:01 [medline]
PHST- 1999/10/09 00:00 [entrez]
AID - 10.1074/jbc.274.42.30001 [doi]
PST - ppublish
SO  - J Biol Chem. 1999 Oct 15;274(42):30001-7. doi: 10.1074/jbc.274.42.30001.