Agmatine induces mitophagy via the PTS-I2R pathway to increase autophagic flux and attenuate sepsis-induced intestinal epithelial cell apoptosis.

Authors

He Jin, Shuangqin Yin, Yongming Li, Xiangwei Hou, Lin Qiao, Tianyin Kuang, Jing Zhou, Xue Yang, Wanting Zeng, Chao Fan, Li Luo, Lihui Wang, Hongyan Xiao, Shengxiang Ao, Shan Su, Quanwei Bao, Yibin Ouyang, Huaping Liang, Junyu Zhu

Published in

Inflammation research : official journal of the European Histamine Research Society ... [et al.]. Volume 75. Issue 1. Jul 06, 2026. Epub Jul 06, 2026.

Abstract

The therapeutic options for sepsis-induced intestinal injury, which drives multiple organ dysfunction and mortality, are limited, but the role of polyamine supplements remains unclear. This study aimed to elucidate the protective effect of agmatine (AGM) on sepsis-induced intestinal injury and its mitochondrial-targeted antiapoptotic mechanism in intestinal epithelial cells (IECs).
We verified the transport and subcellular localization of AGM in IECs via fluorescence assays and established in vitro and in vivo IEC apoptosis models. Functional evaluations using cell viability assays, laser confocal imaging, flow cytometry, transmission electron microscopy, and multiomics techniques were performed.
AGM attenuated sepsis-induced intestinal injury, as evidenced by its ability to lower the serum levels of intestinal damage markers in septic mice, attenuate inflammatory factor production and pathological damage in the intestine, and reduce IEC apoptosis. AGM entered IECs via the polyamine transport system (PTS), but not the NMDA receptor, and inhibited IEC apoptosis induced by TNFα/CHX or TNFα/ActD. Notably, AGM exerted its antiapoptotic effect by targeting the mitochondrial imidazoline I2 receptor (I2R). Mechanistically, AGM induced mitophagy by decreasing the mitochondrial membrane potential without altering mitochondrial number or function, as ROS production, calcium ion influx, ATP generation, and oxygen consumption were unchanged. AGM also increased autophagic flux, as confirmed upon treatment with various autophagy inhibitors.
AGM alleviates sepsis-induced intestinal injury via the PTS-I2R axis by promoting mitophagy and autophagic flux to inhibit IEC apoptosis, laying a foundation for the use of AGM as a potential nutritional supplement or therapeutic agent for sepsis-induced intestinal injury.

PMID:
42406105
Bibliographic data and abstract were imported from PubMed on 06 Jul 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.