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通过组织蛋白酶活性测量评估骨骼肌溶酶体功能

Skeletal Muscle Lysosomal Function via Cathepsin Activity Measurement.

作者信息

Gumpper Kristyn, Sermersheim Matthew, Zhu Michael X, Lin Pei-Hui

机构信息

Davis Heart and Lung Research Institute, The Ohio State University, Columbus, OH, 43210, USA.

Department of Surgery, The Ohio State University Wexner Medical Center, Columbus, OH, 43210, USA.

出版信息

Methods Mol Biol. 2019;1854:35-43. doi: 10.1007/7651_2017_64.

DOI:10.1007/7651_2017_64
PMID:28842895
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5828979/
Abstract

Muscle wasting or cachexia is commonly associated with aging and many diseases such as cancer, infection, autoimmune disorders, and trauma. Decrease in muscle mass, or muscle atrophy, is often caused by dysfunction of protein proteolytic systems, such as lysosomes, which regulate protein turnover and homeostasis. Lysosomes contain many hydrolases and proteases and, thus, represent the major organelle that control protein turnover. Recently, lysosomes have emerged as a signaling hub to integrate cellular functions of nutrient sensing and metabolism, autophagy, phagocytosis, and endocytosis, which are all related to tissue homeostasis. In this chapter, we describe the protocol used to measure lysosomal proteinase (cathepsins) activity in the skeletal muscle. A better understanding of lysosomal function in muscle homeostasis is critical in developing new therapeutic approaches to prevent muscle wasting.

摘要

肌肉萎缩或恶病质通常与衰老以及许多疾病相关,如癌症、感染、自身免疫性疾病和创伤。肌肉质量的减少,即肌肉萎缩,通常是由蛋白质水解系统功能障碍引起的,如溶酶体,其调节蛋白质周转和内环境稳定。溶酶体含有许多水解酶和蛋白酶,因此是控制蛋白质周转的主要细胞器。最近,溶酶体已成为整合营养感知与代谢、自噬、吞噬作用和胞吞作用等细胞功能的信号枢纽,所有这些都与组织内环境稳定相关。在本章中,我们描述了用于测量骨骼肌中溶酶体蛋白酶(组织蛋白酶)活性的方法。更好地理解溶酶体在肌肉内环境稳定中的功能对于开发预防肌肉萎缩的新治疗方法至关重要。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/b28e6675ba43/nihms922090f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/64732b5025cd/nihms922090f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/fb69044811e5/nihms922090f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/b28e6675ba43/nihms922090f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/64732b5025cd/nihms922090f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/fb69044811e5/nihms922090f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ac67/5828979/b28e6675ba43/nihms922090f3.jpg

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本文引用的文献

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Molecular mechanism of sarcopenia and cachexia: recent research advances.肌肉减少症和恶病质的分子机制:最新研究进展
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Autophagy is induced in the skeletal muscle of cachectic cancer patients.恶病质癌症患者的骨骼肌中会诱导自噬。
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Lysosomal cathepsins and their regulation in aging and neurodegeneration.溶酶体组织蛋白酶及其在衰老和神经退行性变中的调控。
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Lysosomal two-pore channel subtype 2 (TPC2) regulates skeletal muscle autophagic signaling.溶酶体双孔通道亚型2(TPC2)调节骨骼肌自噬信号传导。
J Biol Chem. 2015 Feb 6;290(6):3377-89. doi: 10.1074/jbc.M114.608471. Epub 2014 Dec 5.
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Impairment of autophagic flux promotes glucose reperfusion-induced neuro2A cell death after glucose deprivation.自噬流的损伤促进葡萄糖剥夺后葡萄糖再灌注诱导的神经 2A 细胞死亡。
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