杆菌的CagA介导的乙脂生物合成促进了胃癌中的铁灭易感性
Yanmei Peng1, Xuetao Lei1, Qingbin Yang1
1Department of General Surgery & Guangdong Provincial Key Laboratory of Precision Medicine for Gastrointestinal Tumor, Nanfang Hospital, The First School of Clinical Medicine, Southern Medical University, Guangzhou, Guangdong, 510515, China.
Experimental & molecular medicine
|February 21, 2024
概括
杆菌的CagA蛋白使胃癌细胞通过增加特定的脂来易受铁亡. 这一发现表明,CagA状态可以指导阿帕蒂尼布治疗决策.
科学领域:
- 在瘤学瘤学.
- 微生物学 微生物学
- 细胞生物学 细胞生物学
背景情况:
- 杆菌,特别是CagA阳性菌株,与胃癌 (GC) 的进展有关.
- 脂质过氧化驱动的细胞死亡形式铁死与疾病有关,但其与癌症中CagA的关系尚不清楚.
研究的目的:
- 调查CagA在胃癌细胞铁亡中的作用.
- 阐明CagA影响铁亡的分子机制.
- 评估CagA状态在胃癌中的治疗影响.
主要方法:
- 进行了体外和体内实验.
- 进行了基因表达分析 (AGPS,AGPAT3) 和途径分析 (MEK/ERK/SRF).
- 细胞对铁和阿帕蒂尼布的敏感性是根据CagA状态进行评估的.
主要成果:
- 在胃癌细胞中,CagA赋予了对铁亡的敏感性.
- CagA对AGPS和AGPAT3进行上调,促进多不和乙太脂合成和铁亡.
- 在MEK/ERK/SRF路径中,SRF与AGPS促进体结合,调解这种易感性.
- CagA阳性细胞对阿帕蒂尼布的敏感性增加.
结论:
- 通过MEK/ERK/SRF通路和AGPS/AGPAT3上调调节,CagA促进胃癌细胞铁亡.
- H. pylori CagA 状态可以作为分层治疗阿帕蒂尼布患者的生物标志物.
相关概念视频
Gastritis-II: Pathophysiology
326
Gastritis is marked by disruption of the mucosal barrier that usually protects the stomach tissue from digestive juices and manifests in acute and chronic forms.
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
In acute gastritis, the gastric mucosa becomes swollen and red and undergoes superficial erosion. Superficial ulceration may lead to bleeding.
In chronic gastritis, persistent or repeated insults lead to chronic inflammatory changes and, eventually, thinning or atrophy of the gastric tissue.
Gastritis can stem from various causes, each...
326
Treating Helicobacter pylori in Peptic Ulcers: Antimicrobial Therapy
403
Helicobacter pylori, a resilient gram-negative bacterium, can thrive in the stomach's harsh, acidic environment. Infection with H. pylori leads to a cascade of events within the stomach lining. One of the critical disruptions caused by this bacterium is the interference with somatostatin production, a hormone responsible for regulating acid secretion. This interference tips the balance, escalating acid secretion and diminishing bicarbonate levels. This imbalance compromises the defensive...
403
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
Peptic Ulcer Disease I: Introduction
168
Peptic Ulcer Disease (PUD) is characterized by mucosal excavation in the esophagus, stomach, pylorus, or duodenum. It can manifest as acute or chronic based on the extent and duration of mucosal involvement.
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
An acute ulcer, marked by superficial erosion and minimal inflammation, swiftly resolves upon identifying and addressing the underlying cause. In contrast, a chronic ulcer persists, potentially eroding through the muscular wall and forming fibrous tissue.
Peptic ulcers can also be...
168
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
Export of Misfolded Proteins out of the ER
3.6K
After folding, the ER assesses the quality of secretory and membrane proteins. The correctly folded proteins are cleared by the calnexin cycle for transport to their final destination, while misfolded proteins are held back in the ER lumen. The ER chaperones attempt to unfold and refold the misfolded proteins but sometimes fail to achieve the correct native conformation. Such terminally misfolded proteins are then exported to the cytosol by ER-associated degradation or ERAD pathway for...
3.6K


