PMID- 19115269
OWN - NLM
STAT- MEDLINE
DCOM- 20090323
LR  - 20111117
IS  - 1097-4644 (Electronic)
IS  - 0730-2312 (Linking)
VI  - 106
IP  - 3
DP  - 2009 Feb 15
TI  - Insulin induces the low density lipoprotein receptor-related protein 1 (LRP1) 
      degradation by the proteasomal system in J774 macrophage-derived cells.
PG  - 372-80
LID - 10.1002/jcb.22014 [doi]
AB  - Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic 
      receptor, which binds and internalizes diverse ligands such as activated 
      alpha(2)-macroglobulin (alpha(2)M*). LRP1 promotes intracellular signaling, which 
      downstream mediates cellular proliferation and migration of different types of 
      cells, including macrophages. Unlike the LDL receptor, LRP1 expression is not 
      sensitive to cellular cholesterol levels but appears to be responsive to insulin. 
      It has been previously demonstrated that insulin increases the cell surface 
      presentation of LRP1 in adipocytes and hepatocytes, which is mediated by the 
      intracellular PI(3)K/Akt signaling activation. The LRP1 protein distribution is 
      similar to other insulin-regulated cell surface proteins, including transferring 
      receptor (Tfr). However, in macrophages, the insulin effect on the LRP1 
      distribution and expression is not well characterized. Considering that 
      macrophages play a central role in the pathogenesis of atherosclerosis, herein we 
      evaluate the effect of insulin on the cellular expression of LRP1 in J774 
      macrophages-derived cells using Western blot and immunofluorescence microscopy. 
      Our data demonstrate that insulin induces a significant decrease in the LRP1 
      protein content, without changing the specific mRNA level of this receptor. 
      Moreover, insulin specifically affected the protein expression of LRP1 but not 
      Tfr. The insulin-induced protein degradation of LRP1 in J774 cells was mediated 
      by the activation of the PI(3)K/Akt pathway and proteasomal system by an enhanced 
      ubiquitin-receptor conjugation. The decreased content of LRP1 induced by insulin 
      affected the cellular internalization of alpha(2)M*. Thus, we propose that the 
      protein degradation of LRP-1 induced by insulin in macrophages could have 
      important effects on the pathogenesis of atherosclerosis.
FAU - Ceschin, Danilo G
AU  - Ceschin DG
AD  - Centro de Investigaciones en Bioquimica Clinica e Inmunologia (CIBICI)-CONICET, 
      Departamento de Bioquimica Clinica, Facultad de Ciencias Quimicas, Universidad 
      Nacional de Cordoba, 5000 Cordoba, Argentina.
FAU - Sanchez, Maria C
AU  - Sanchez MC
FAU - Chiabrando, Gustavo A
AU  - Chiabrando GA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Cell Biochem
JT  - Journal of cellular biochemistry
JID - 8205768
RN  - 0 (Insulin)
RN  - 0 (Low Density Lipoprotein Receptor-Related Protein-1)
RN  - 0 (alpha-Macroglobulins)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.25.1 (Proteasome Endopeptidase Complex)
SB  - IM
MH  - Animals
MH  - Cell Line
MH  - Gene Expression Regulation/genetics
MH  - Insulin/*pharmacology
MH  - Low Density Lipoprotein Receptor-Related Protein-1/genetics/*metabolism
MH  - Macrophages/cytology/*drug effects/*metabolism
MH  - Mice
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Proteasome Endopeptidase Complex/*metabolism
MH  - Protein Transport
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Signal Transduction
MH  - alpha-Macroglobulins/metabolism
EDAT- 2008/12/31 09:00
MHDA- 2009/03/24 09:00
CRDT- 2008/12/31 09:00
PHST- 2008/12/31 09:00 [entrez]
PHST- 2008/12/31 09:00 [pubmed]
PHST- 2009/03/24 09:00 [medline]
AID - 10.1002/jcb.22014 [doi]
PST - ppublish
SO  - J Cell Biochem. 2009 Feb 15;106(3):372-80. doi: 10.1002/jcb.22014.