Ke Wang, Bochuan Yuan, Feng Zhang, Zhangyu Li, Xueli Jia, Yadan Hu, Ziyuan Chen, Jinyun Hong, Lina Du, Yiguang Jin
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引用次数: 0
Abstract
The scavenging of the excess reactive oxygen species (ROS) induced by radiation is fundamental for radiation protection. However, directly applying antioxidants results in low bioavailability and side effects. Superoxide dismutase (SOD) and catalase (CAT) have high ROS clearance efficiency, whereas their application is limited by the enzyme inactivation, making it difficult to exhibit significant therapeutic effects. Here, we engineered a probiotic Escherichia coli Nissle 1917 (EcN), i.e., AAEcN, serving as a SOD/CAT vehicle to scavenge ROS for the prevention and treatment of radiation enteritis (RE). The overexpressed Drsod and katE in AAEcN showed 5-fold ROS elimination efficiency compared to the wild EcN. Furthermore, the intestinal retention time of engineered EcN was prolonged through trefoil factor 3 gene (TFF3) modification of curli fibers on the bacterial surface, which contributed to the persistence of antioxidant enzyme activity. We found that AAEcN rapidly eliminated the intracellular ROS induced by radiation. Only a single oral dosing of AAEcN was satisfied to alleviate the radiation damage to the small intestine, colon, and spleen. Moreover, the homeostasis of pro-/anti-inflammatory cytokines was realized. The proliferation of the intestinal stem cells and spleen hematopoietic stem cells was enhanced, while the apoptosis of mucosal cells was inhibited. Our findings suggest valuable insights into the ROS scavenging way in RE, and establish an empirical basis for developing probiotics as an antioxidant enzyme vehicle for the bacteriotherapy of RE.
期刊介绍:
Free Radical Biology and Medicine is a leading journal in the field of redox biology, which is the study of the role of reactive oxygen species (ROS) and other oxidizing agents in biological systems. The journal serves as a premier forum for publishing innovative and groundbreaking research that explores the redox biology of health and disease, covering a wide range of topics and disciplines. Free Radical Biology and Medicine also commissions Special Issues that highlight recent advances in both basic and clinical research, with a particular emphasis on the mechanisms underlying altered metabolism and redox signaling. These Special Issues aim to provide a focused platform for the latest research in the field, fostering collaboration and knowledge exchange among researchers and clinicians.