Hepatic disposal of advanced glycation end products during maturation and aging.
Hepatic disposal of advanced glycation end products during maturation and aging.
复制标题
成熟和衰老过程中晚期糖基化终产物的肝脏处理。
DOI：
10.1016/j.exger.2013.03.005
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发表时间：
2013-06
影响因子：
3.9
通讯作者：
Smedsrød B
中科院分区：
文献类型：
--
作者：
Svistounov D;Oteiza A;Zykova SN;Sørensen KK;McCourt P;McLachlan AJ;McCuskey RS;Smedsrød B
衰老的特征是代谢和生化功能的逐渐丧失以及代谢副产物的积累，包括晚期糖基化终产物（AGEs），这在几种病理条件下都可以观察到。包括AGEs在内的许多废物大分子通过内吞作用从循环中被吸收，主要进入肝窦内皮细胞（LSECs）和库普弗细胞（KCs）。然而，尽管存在这种清除机制，随着年龄的增长，AGEs仍然在不同组织中积累。本研究的目的是确定LSECs和KCs处理AGEs的效率是否随着年龄的增长而变化。在青春期前、青壮年、中年和老年小鼠静脉注射14C-AGE白蛋白后，90%以上恢复的14C-AGE与肝脏相关，与年龄无关。LSECs和KCs是主要的摄取部位。一部分14C-AGE降解产物（14C-AGE- dps）在摄取后在这些细胞的溶酶体中储存数月。在青春期前，肝脏中14C-AGE-DPs的清除速度明显快于所有青春期后年龄组。LSECs和KCs在青春期后消除14C-AGE-DPs的能力下降的程度相似。快速早期切除阶段是所有年龄组的特征，除了老年组，这一阶段不存在。从肝脏清道夫细胞中去除age - dps是一个非常缓慢的过程，随着年龄的增长而变化。这些细胞处理AGEs的能力在青春期后下降。早期AGE去除效率降低可能导致AGE积累。
Aging is characterized by progressive loss of metabolic and biochemical functions and accumulation of metabolic by-products, including advanced glycation end products (AGEs), which are observed in several pathological conditions. A number of waste macromolecules, including AGEs are taken up from the circulation by endocytosis mainly into liver sinusoidal endothelial cells (LSECs) and Kupffer cells (KCs). However, AGEs still accumulate in different tissues with ageing, despite the presence of this clearance mechanism. The aim of the present study was to determine whether the efficiency of LSECs and KCs for disposal of AGEs changes through aging. After intravenous administration of 14C-AGE-albumin in pre-pubertal, young adult, middle aged and old mice, more than 90% of total recovered 14C-AGE was liver associated, irrespective of age. LSECs and KCs represented the main site of uptake. A fraction of the 14C-AGE degradation products (14C-AGE-DPs) was stored for months in the lysosomes of these cells after uptake. The overall rate of elimination of 14C-AGE-DPs from the liver was markedly faster in pre-pubertal than in all post-pubertal age groups. The ability to eliminate 14C-AGE-DPs decreased to similar extents after puberty in LSECs and KCs. A rapid early removal phase was characteristic for all age groups except the old group, where this phase was absent. Removal of AGE-DPs from the liver scavenger cells is a very slow process that changes with age. The ability of these cells to dispose of AGEs declines after puberty. Decreased AGE removal efficiency early in life may lead to AGE accumulation.
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影响因子：
4.1
作者：
Smedsrod, B;Melkko, J;Horiuchi, S
通讯作者：
Horiuchi, S
DOI：
10.1073/pnas.93.1.485
发表时间：
1996-01-09
影响因子：
11.1
作者：
Sell, DR;Lane, MA;Monnier, VM
通讯作者：
Monnier, VM
影响因子：
15.9
作者：
Schleicher, ED;Wagner, E;Nerlich, AG
通讯作者：
Nerlich, AG
影响因子：
64.5
作者：
ROME, LH;GARVIN, AJ;NEUFELD, EF
通讯作者：
NEUFELD, EF
影响因子：
11.8
作者：
Medina, Diego L.;Fraldi, Alessandro;Bouche, Valentina;Annunziata, Fabio;Mansueto, Gelsomina;Spampanato, Carmine;Puri, Claudia;Pignata, Antonella;Martina, Jose A.;Sardiello, Marco;Palmieri, Michela;Polishchuk, Roman;Puertollano, Rosa;Ballabio, Andrea
通讯作者：
Ballabio, Andrea