CIBICI   14215
CENTRO DE INVESTIGACION EN BIOQUIMICA CLINICA E INMUNOLOGIA
Unidad Ejecutora - UE
artículos
Título:
"Insulin Induces the Low Density Lipoprotein Receptor-Related Protein (LRP-1) Degradation by the Proteasomal System in J774 Macrophage-Derived Cells."
Autor/es:
CESCHIN D; SANCHEZ MC,; CHIABRANDO GA
Revista:
JOURNAL OF CELLULAR BIOCHEMISTRY
Editorial:
WILEY-LISS, DIV JOHN WILEY & SONS INC
Referencias:
Año: 2009 vol. 106 p. 372 - 380
ISSN:
0730-2312
Resumen:
Low-density lipoprotein receptor-related protein 1 (LRP1) is an endocytic receptor, which binds and internalizes diverse ligands such as
activated a2-macroglobulin (a2M). 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 PI3K/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 PI3K/Akt pathway and proteasomal system by
an enhanced ubiquitinreceptor conjugation. The decreased content of LRP1 induced by insulin affected the cellular internalization of a2M.
Thus, we propose that the protein degradation of LRP-1 induced by insulin in macrophages could have important effects on the pathogenesis
of atherosclerosis.a2-macroglobulin (a2M). 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 PI3K/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 PI3K/Akt pathway and proteasomal system by
an enhanced ubiquitinreceptor conjugation. The decreased content of LRP1 induced by insulin affected the cellular internalization of a2M.
Thus, we propose that the protein degradation of LRP-1 induced by insulin in macrophages could have important effects on the pathogenesis
of atherosclerosis.3K/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 PI3K/Akt pathway and proteasomal system by
an enhanced ubiquitinreceptor conjugation. The decreased content of LRP1 induced by insulin affected the cellular internalization of a2M.
Thus, we propose that the protein degradation of LRP-1 induced by insulin in macrophages could have important effects on the pathogenesis
of atherosclerosis.3K/Akt pathway and proteasomal system by
an enhanced ubiquitinreceptor conjugation. The decreased content of LRP1 induced by insulin affected the cellular internalization of a2M.
Thus, we propose that the protein degradation of LRP-1 induced by insulin in macrophages could have important effects on the pathogenesis
of atherosclerosis.a2M.
Thus, we propose that the protein degradation of LRP-1 induced by insulin in macrophages could have important effects on the pathogenesis
of atherosclerosis.