Liu Yun, Miao Renjie, Xia Jinxuan, Zhou Yong, Yao Jun, Shao Shihe
Department of Gastroenterology, Institute of Digestive Disease, The Affiliated People's Hospital, Jiangsu University, Zhenjiang, Jiangsu, China.
School of Medicine, Jiangsu University, Zhenjiang, Jiangsu, China.
Cell Death Discov. 2024 Dec 2;10(1):485. doi: 10.1038/s41420-024-02253-3.
Helicobacter pylori (H. pylori) is a gram-negative pathogen that colonizes gastric epithelial cells, and its chronic infection is the primary risk factor for the development of gastric cancer (GC). Ferroptosis is an iron-dependent form of cell death characterized by intracellular lipid peroxide accumulation and reactive oxygen species (ROS) imbalance. There is evidence suggesting that pathogens can manipulate ferroptosis to facilitate their replication, transmission, and pathogenesis. However, the interaction between ferroptosis and H. pylori infection requires further elucidation. We reviewed the mechanism of ferroptosis and found that H. pylori virulence factors such as cytotoxin-associated gene A (CagA), vacuolating cytotoxin A (VacA), neutrophil-activating protein A (NapA), superoxide dismutase B (SodB), γ-glutamyl transpeptidase (gGT), lipopolysaccharide (LPS), and outer inflammatory protein A (OipA) affected glutathione (GSH), ROS, and lipid oxidation to regulate ferroptosis. It also affected the progression of GC by regulating ferroptosis-related indicators through abnormal gene expression after H. pylori infected gastric mucosa cells. Finally, we discuss the potential application value of ferroptosis inducers, inhibitors and other drugs in treating H. pylori-infected GC patients while acknowledging that their interactions are still not fully understood.
幽门螺杆菌（H. pylori）是一种定殖于胃上皮细胞的革兰氏阴性病原体，其慢性感染是胃癌（GC）发生的主要危险因素。铁死亡是一种铁依赖性细胞死亡形式，其特征是细胞内脂质过氧化物积累和活性氧（ROS）失衡。有证据表明，病原体可以操纵铁死亡以促进其复制、传播和发病机制。然而，铁死亡与幽门螺杆菌感染之间的相互作用仍需进一步阐明。我们综述了铁死亡的机制，发现幽门螺杆菌的毒力因子，如细胞毒素相关基因A（CagA）、空泡毒素A（VacA）、中性粒细胞激活蛋白A（NapA）、超氧化物歧化酶B（SodB）、γ-谷氨酰转肽酶（gGT）、脂多糖（LPS）和外炎症蛋白A（OipA），会影响谷胱甘肽（GSH）、ROS和脂质氧化，从而调节铁死亡。幽门螺杆菌感染胃黏膜细胞后，还通过异常基因表达调节铁死亡相关指标，进而影响胃癌的进展。最后，我们讨论了铁死亡诱导剂、抑制剂和其他药物在治疗幽门螺杆菌感染的胃癌患者中的潜在应用价值，同时承认它们之间的相互作用仍未完全了解。
