Increased Expression of Cathepsins E and D in Neurons of the Aged Rat Brain and Their Colocalization with Lipofuscin and Carboxy‐Terminal Fragments of Alzheimer Amyloid Precursor Protein
Increased Expression of Cathepsins E and D in Neurons of the Aged Rat Brain and Their Colocalization with Lipofuscin and Carboxy‐Terminal Fragments of Alzheimer Amyloid Precursor Protein
复制标题
老年大鼠脑神经元中组织蛋白酶 E 和 D 的表达增加及其与脂褐素和阿尔茨海默淀粉样前体蛋白羧基末端片段的共定位
DOI：
--
复制
发表时间：
1997
影响因子：
4.7
通讯作者：
Kenji Yamamoto
中科院分区：
文献类型：
--
作者：
H. Nakanishi;Tutomu Amano;Dewi F. Sastradipura;Y. Yoshimine;T. Tsukuba;Kazunari Tanabe;I. Hirotsu;Tomochika Ohono;Kenji Yamamoto
摘要：采用免疫细胞化学和定量方法研究了大鼠大脑皮层和脑干两种不同的细胞内天冬氨酸蛋白酶组织蛋白酶E （CE）和组织蛋白酶D （CD）在年龄相关的表达和定位变化。非溶酶体CE在胚胎期的两种脑组织中几乎检测不到，而在胚胎期组织中溶酶体CD的表达相对较高。出生后，CE在这些组织中的表达随着年龄的增长而增加，在30月龄时达到最高水平。Western blot分析显示，在2月龄和17月龄时，CE主要以成熟酶的形式存在，而在30月龄时，CE不仅以成熟酶的形式存在，而且以原酶的形式存在。另一方面，CD主要存在于整个发育过程中的成熟形态中，尽管其在这些组织中的水平也随着年龄的增长而显著增加。老年大鼠皮层和脑干神经元的CE阳性与脂质自发荧光细胞相对应。通过双染色技术，大多数老年大鼠皮层和脑干神经元的CE阳性抗体也呈淀粉样蛋白前体蛋白羧基末端片段（APP634-695）抗体阳性，该抗体的细胞内积累被认为与内核/溶酶体系统的年龄相关变化有关。重要的是，电镜显示老年大鼠脑干神经元中的CE与含脂褐素溶酶体中的CD共定位。这些结果表明，衰老导致皮质和脑干神经元中CE的表达和溶酶体定位增加，内体/溶酶体蛋白水解系统发生改变，这可能与脂质褐变和细胞内APP代谢改变有关。
Abstract: Age‐related changes in the expression and localization of two distinct intracellular aspartic proteinases, cathepsin E (CE) and cathepsin D (CD), were investigated in the rat cerebral cortex and the brainstem by immunocytochemical and quantitative methods using discriminative antibodies specific for each enzyme. Non‐lysosomal CE was barely detectable in these two brain tissues in the embryonic stages, whereas relatively high expression of lysosomal CD was observed in embryonic tissues. After birth, CE was increasingly expressed in these tissues with aging to attain maximal levels at 30 months of age. Western blot analyses revealed that CE existed predominantly as the mature enzyme at 2 and 17 months of age, whereas it was present as not only the mature enzyme but also the proenzyme at 30 months of age. On the other hand, CD was mainly present in the mature form throughout development, although its level in these tissues was also significantly increased with aging. The CE‐positive cortical and brainstem neurons of the aged rat corresponded well with cells emitting autofluorescence for lipopigments. By the double‐staining technique, most of the CE‐positive cortical and brainstem neurons of the aged rat were also positive for antibody to the carboxyl‐terminal fragments of amyloid precursor protein (APP634–695), intracellular accumulation of which is thought to be associated with age‐related changes in the endosome/lysosome system. It is important that electron microscopy revealed that CE in brainstem neurons of the aged rat colocalized with CD in the lipofuscin‐containing lysosomes. These results indicate that aging results in the increased expression and lysosomal localization of CE in cortical and brainstem neurons and changes in the endosomal/lysosomal proteolytic system, which may be related to lipofuscinogenesis and altered intracellular APP metabolism.
登录
查看更多内容
影响因子：
56.9
作者：
IVY, GO;SCHOTTLER, F;LYNCH, G
通讯作者：
LYNCH, G
组织蛋白酶 E 的亚细胞定位和靶向。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Finley,EM;Kornfeld,S
通讯作者：
Kornfeld,S
组织蛋白酶 D 在阿尔茨海默氏病淀粉样蛋白-β 的氨基和羧基末端进行切割。
DOI：
--
发表时间：
1994
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ladror,US;Snyder,SW;Wang,GT;Holzman,TF;Krafft,GA
通讯作者：
Krafft,GA
DOI：
10.1073/pnas.88.24.10998
发表时间：
1991-12-01
影响因子：
11.1
作者：
CATALDO, AM;PASKEVICH, PA;NIXON, RA
通讯作者：
NIXON, RA