Insulin Enhances Macrophage Scavenger Receptor-mediated Endocytic Uptake of Advanced Glycation End Products
| Autor: | Yoshiteru Jinnouchi, Kazuyoshi Ikeda, Kenshi Matsumoto, Jukka Melkko, Takayuki Higashi, Hiroyuki Sano, Hideichi Makino, Yousuke Ebina, Seikoh Horiuchi, Bård Smedsrød |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Glycation End Products
Advanced medicine.medical_treatment Endocytic cycle Biochemistry Wortmannin chemistry.chemical_compound Cricetinae Insulin LY294002 Enzyme Inhibitors Receptors Immunologic Receptor Cells Cultured Receptors Scavenger Chinese hamster ovary cell Serum Albumin Bovine Scavenger Receptors Class B Endocytosis Cell biology Lipoproteins LDL Liver medicine.medical_specialty Morpholines Recombinant Fusion Proteins CHO Cells Polyenes Biology Transfection Models Biological Cell Line Internal medicine medicine Animals Humans Scavenger receptor Molecular Biology Receptors Lipoprotein Sirolimus Macrophages Membrane Proteins Cell Biology Receptor Insulin Rats Androstadienes Kinetics Insulin receptor Endocrinology chemistry Chromones biology.protein Endothelium Vascular |
| Zdroj: | Journal of Biological Chemistry. 273:8630-8637 |
| ISSN: | 0021-9258 |
| Popis: | Hyperglycemia accelerates the formation and accumulation of advanced glycation end products (AGE) in plasma and tissue, which may cause diabetic vascular complications. We recently reported that scavenger receptors expressed by liver endothelial cells (LECs) dominantly mediate the endocytic uptake of AGE proteins from plasma, suggesting its potential role as an eliminating system for AGE proteins in vivo (Smedsrod, B., Melkko, J., Araki, N., Sano, H., and Horiuchi, S. (1997) Biochem. J. 322, 567-573). In the present study we examined the effects of insulin on macrophage scavenger receptor (MSR)-mediated endocytic uptake of AGE proteins. LECs expressing MSR showed an insulin-sensitive increase of endocytic uptake of AGE-bovine serum albumin (AGE-BSA). Next, RAW 264.7 cells expressing a high amount of MSR were overexpressed with human insulin receptor (HIR). Insulin caused a 3.7-fold increase in endocytic uptake of 125I-AGE-BSA by these cells. The effect of insulin was inhibited by wortmannin, a phosphatidylinositol-3-OH kinase (PI3 kinase) inhibitor. To examine at a molecular level the relationship between insulin signal and MSR function, Chinese hamster ovary (CHO) cells expressing a negligible level of MSR were cotransfected with both MSR and HIR. Insulin caused a 1.7-fold increase in the endocytic degradation of 125I-AGE-BSA by these cells, the effect of which was also inhibited by wortmannin and LY294002, another PI3 kinase inhibitor. Transfection of CHO cells overexpressing MSR with two HIR mutants, a kinase-deficient mutant, and another lacking the binding site for insulin receptor substrates (IRS) resulted in disappearance of the stimulatory effect of insulin on endocytic uptake of AGE proteins. The present results indicate that insulin may accelerate MSR-mediated endocytic uptake of AGE proteins through an IRS/PI3 kinase pathway. |
| Databáze: | OpenAIRE |
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