蛋白酶体功能的降低会增加氧化应激在压力发育的早期阶段
Eri Murata1, Takuma Yoshida2, Utano Tomaru3
1Department of Pathology, Faculty of Medicine and Graduate School of Medicine, Hokkaido University, Kita-ku, Sapporo, Japan; Department of Fundamental Nursing, Yamagata University Graduate School of Nursing, Yamagata, Yamagata, Japan.
Experimental and molecular pathology
|March 10, 2024
概括
衰老会降低蛋白质酶的功能,增加氧化应激和老年人皮肤损伤的风险. 像EDARAVONE这样的自由基掠食者,通过减轻与年龄相关的损害,有望防止压力的发展.
科学领域:
- 老年学是一门学科.
- 皮肤病学 皮肤病学
- 分子生物学分子生物学
背景情况:
- 老龄化增加了皮肤的脆弱性和对压力 (PUs) 的易感性.
- 衰老对PU病变的具体影响,特别是关于蛋白质酶功能和氧化应激,需要进一步研究.
- 缺血-再输液 (I/R) 损伤和反应性氧物种 (ROS) 是PU发展的关键早期因素.
研究的目的:
- 调查与年龄相关的蛋白酶体活性下降对皮肤缺血-再输液 (I/R) 损伤的作用.
- 确定蛋白酶抑制对氧化应激和皮肤中Nrf2介导的抗氧化反应的影响.
- 评估自由基清除剂在减轻与年龄有关的皮肤损伤方面的治疗潜力.
主要方法:
- 利用与年龄相关的蛋白质体功能障碍的小鼠模型在体内研究皮肤I/R损伤.
- 检查了炎症性细胞因子和粘附分子后I / R的表达.
- 评估了皮肤纤维细胞在低氧-重氧化 (H/R) 条件下与蛋白质酶抑制的氧化应激,ROS产生和抗氧化酶表达.
- 研究了自由基捕食者edaravone的保护作用.
主要成果:
- 在老年小鼠中,蛋白质酶抑制并没有改变炎症标志物,但显著增加了氧化应激.
- Nrf2激活未能充分抵消蛋白酶抑制细胞中增加的氧化应激.
- 埃达拉在体内证明了对I/R损伤的保护作用,并在体内减少了氧化应激.
- 与年龄相关的蛋白质酶活性下降加剧了I/R诱导的氧化应激.
结论:
- 与衰老相关的蛋白质酶活性降低通过增加氧化应激促进皮肤I / R损伤.
- 由Nrf2介导的抗氧化反应可能不足以克服蛋白质酶功能障碍引起的氧化应激.
- 自由基捕食者代表了一种潜在的治疗策略,通过控制氧化应激来预防早期的压力.
相关概念视频
The Proteasome
833
Eukaryotic cells can degrade proteins through several pathways. One of the most important among these is the ubiquitin-proteasome pathway. It helps the cell eliminate the misfolded, damaged, or unwarranted cytoplasmic proteins in a highly specific manner.
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
In this pathway, the target proteins are first tagged with small proteins called ubiquitin. This involves participation of a series of enzymes including— E1 (ubiquitin-activating enzyme), E2 (ubiquitin-conjugating enzyme), and E3...
833
Regulation of the Unfolded Protein Response
2.4K
Inositol-requiring kinase one or IRE1 is the most conserved eukaryotic unfolded protein response (UPR) receptor. It is a type I transmembrane protein kinase receptor with a distinctive site-specific RNase activity. As the binding mechanics of the misfolded proteins with the N-terminal domain of IRE-1 are unclear, three binding models — direct, indirect, and allosteric -- are proposed for receptor activation. Nevertheless, it is known that once a misfolded protein associates with IRE1, it...
2.4K
Peptic Ulcer Disease II: Pathophysiology
424
Peptic Ulcer Disease (PUD) is characterized by the development of ulcers in the stomach or duodenal mucosa. Its pathophysiology is complex, involving a balance between damaging and protective elements.
Damaging agents such as Helicobacter pylori, gastric acid, pepsin, and nonsteroidal anti-inflammatory drugs (NSAIDs) can weaken the mucosal defense, allowing hydrogen ions to infiltrate back and harm epithelial cells.
Damaging agents such as Helicobacter pylori, gastric acid, pepsin, and nonsteroidal anti-inflammatory drugs (NSAIDs) can weaken the mucosal defense, allowing hydrogen ions to infiltrate back and harm epithelial cells.
424
Pathophysiology of Peptic Ulcer Disease: Mucosal Defense Factors
429
Peptic ulcer disease, commonly called PUD, represents a multifaceted condition characterized by disruptions in the lining of the gastrointestinal (GI) tract. Central to the protection of the gastrointestinal lining is the mucosal-bicarbonate barrier. This physiological defense mechanism is a formidable shield against the corrosive effects of gastric acid and pepsin secretion in the stomach. Its role is pivotal in maintaining the structural integrity of the stomach's inner lining.
429
Pathophysiology of Peptic Ulcer Disease: Injurious Factors
591
Peptic ulcers are sores on the stomach's inner lining and the upper small intestine, which are the result of disruptions in the mucosal layer that houses parietal cells which produce gastric acid, and chief cells which secrete pepsinogen.
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
In the antrum region, G cells secrete the gastrin hormone that binds to gastrin-cholecystokinin-B (CCK2) receptors on parietal and enterochromaffin-like (ECL) cells in the fundic glands. Simultaneously, the vagus nerve releases acetylcholine, which binds...
591
The Proteasome Structure
752
The ubiquitin-proteasome pathway is a well-known mechanism utilized by eukaryotic cells to remove cytoplasmic proteins that are misfolded, damaged, or no longer needed. In this pathway, the protein that needs to be eliminated undergoes a process called ubiquitination, where a chain of ubiquitin molecules is attached to the 48th lysine residue of the target protein. This ubiquitin modification helps the proteasome distinguish between a target protein and a healthy protein.
The proteasome is an...
The proteasome is an...
752


