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蛋白酶在慢性阻塞性肺疾病中的作用

Role of Proteases in Chronic Obstructive Pulmonary Disease.

作者信息

Pandey Kailash C, De Sajal, Mishra Pradyumna K

机构信息

Department of Biochemistry, National Institute for Research in Environmental Health (ICMR)Bhopal, India.

Department of Pulmonary Medicine, National Institute for Research in Environmental Health (ICMR)Bhopal, India.

出版信息

Front Pharmacol. 2017 Aug 8;8:512. doi: 10.3389/fphar.2017.00512. eCollection 2017.

Abstract

Chronic obstructive pulmonary disease (COPD) is generally associated with progressive destruction of airways and lung parenchyma. Various factors play an important role in the development and progression of COPD, like imbalance of proteases, environmental and genetic factors and oxidative stress. This review is specifically focused on the role of proteases and their imbalance in COPD. There are three classes (serine, mettalo, and cysteine) of proteases involved in COPD. In serine proteases, neutrophil elastase, cathepsin G, and proteinase-3 are involved in destruction of alveolar tissue. Matrix-mettaloproteinase-9, 12, 13, plays an influential role in severity of COPD. Among cysteine proteases, caspase-3, caspases-8 and caspase-9 play an important role in controlling apoptosis. These proteases activities can be regulated by inhibitors like α-1-antitrypsin, neutrophil elastase inhibitor, and leukocyte protease inhibitor. Studies suggest that neutrophil elastase may be a therapeutic target for COPD, and specific inhibitor against this enzyme has potential role to control the disease. Current study suggests that Dipeptidyl Peptidase IV is a potential marker for COPD. Since the expression of proteases and its inhibitors play an important role in COPD pathogenesis, therefore, it is worth investigating the role of proteases and their regulation. Understanding the biochemical basis of COPD pathogenesis using advanced tools in protease biochemistry and aiming toward translational research from bench-to-bedside will have great impact to deal with this health problem.

摘要

慢性阻塞性肺疾病(COPD)通常与气道和肺实质的进行性破坏相关。多种因素在COPD的发生和发展中起重要作用,如蛋白酶失衡、环境和遗传因素以及氧化应激。本综述特别关注蛋白酶及其失衡在COPD中的作用。COPD涉及三类蛋白酶(丝氨酸蛋白酶、金属蛋白酶和半胱氨酸蛋白酶)。在丝氨酸蛋白酶中,中性粒细胞弹性蛋白酶、组织蛋白酶G和蛋白酶-3参与肺泡组织的破坏。基质金属蛋白酶-9、12、13在COPD的严重程度中起重要作用。在半胱氨酸蛋白酶中,半胱天冬酶-3、半胱天冬酶-8和半胱天冬酶-9在控制细胞凋亡中起重要作用。这些蛋白酶的活性可由α-1抗胰蛋白酶、中性粒细胞弹性蛋白酶抑制剂和白细胞蛋白酶抑制剂等抑制剂调节。研究表明,中性粒细胞弹性蛋白酶可能是COPD的治疗靶点,针对该酶的特异性抑制剂在控制疾病方面具有潜在作用。当前研究表明二肽基肽酶IV是COPD的一个潜在标志物。由于蛋白酶及其抑制剂的表达在COPD发病机制中起重要作用,因此,研究蛋白酶及其调节作用是值得的。利用蛋白酶生物化学的先进工具理解COPD发病机制的生化基础,并致力于从 bench 到 bedside 的转化研究,将对解决这一健康问题产生重大影响。

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