RAGE, LDL receptor, and LRP1 expression in the brains of SAMP8.
SAMP8, senescence-accelerated mice with age-related deficits in memory and learning, are known to show age-related increases of amyloid precursor protein (APP) expression and to be under elevated oxidative stress. The receptor for advanced glycation end product (RAGE) is a representative influx transporter of APP or amyloid-beta (A beta) protein in cerebral vessels, while low-density lipoprotein receptor (LDLR) and LDL-related protein 1 (LRP1) are efflux transporters. These receptors play roles not only in clearance of A beta protein but also in control of oxidative stress. In this study, we examined the gene and protein expressions of these receptors, by real-time quantitative reverse transcriptase-polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemical techniques. SAMR1 mice with lower expression of APP were as controls. The gene and protein expressions of RAGE were lower in SAMP8 brains than in SAMR1. Those of LDLR were higher in SAMP8 brains than those of SAMR1. There were no differences in the expressions of LRP1 between SAMP8 and SAMR1. Immunosignals of RAGE and LDLR were seen in the cytoplasm of CD34-positive endothelial cells and also in astrocytes, in both strains of mice. These findings suggest that the lower expression of RAGE and the higher expression of LDLR may contribute to clearance of toxic substances and, in addition, be related to elevated oxidative stress in SAMP8 brains.
Wu
Bin
B
Department of Pathology and Host Defense, Faculty of Medicine, Kagawa University, 1750-1 Ikenobe, Miki-cho, Kita-gun, Kagawa 761-0793, Japan.
Ueno
Masaki
M
Onodera
Masayuki
M
Kusaka
Takashi
T
Huang
Cheng-long
CL
Hosomi
Naohisa
N
Kanenishi
Kenji
K
Sakamoto
Haruhiko
H
D000375:Aging / Q000378:metabolism; D016564:Amyloid beta-Protein Precursor / Q000096:biosynthesis; D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D001921:Brain / Q000098:blood supply / Q000378:metabolism*; D042783:Endothelial Cells / Q000378:metabolism; D007150:Immunohistochemistry; D026503:Low Density Lipoprotein Receptor-Related Protein-1; D008297:Male; D051379:Mice; D018613:Microscopy, Confocal; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic / Q000096:biosynthesis* / Q000235:genetics; D011973:Receptors, LDL / Q000096:biosynthesis* / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
D016564:Amyloid beta-Protein Precursor; D026503:Low Density Lipoprotein Receptor-Related Protein-1; C486645:Lrp1 protein, mouse; D000067759:Receptor for Advanced Glycation End Products; D011971:Receptors, Immunologic; D011973:Receptors, LDL; D025521:Tumor Suppressor Proteins