Excessive Apoptosis in Ulcerative Colitis: Crosstalk Between Apoptosis, ROS, ER Stress, and Intestinal Homeostasis

Abstract

Ulcerative colitis (UC), an etiologically complicated and relapsing gastrointestinal disease, is characterized by the damage of mucosal epithelium and destruction of the intestinal homeostasis, which has caused a huge social and economic burden on the health system all over the world. Its pathogenesis is multifactorial, including environmental factors, genetic susceptibility, epithelial barrier defect, symbiotic flora imbalance, and dysregulated immune response. Thus far, although immune cells have become the focus of most research, it is increasingly clear that intestinal epithelial cells play an important role in the pathogenesis and progression of UC. Notably, apoptosis is a vital catabolic process in cells, which is crucial to maintain the stability of intestinal environment and regulate intestinal ecology. In this review, the mechanism of apoptosis induced by reactive oxygen species and endoplasmic reticulum stress, as well as excessive apoptosis in intestinal epithelial dysfunction and gut microbiology imbalance are systematically and comprehensively summarized. Further understanding the role of apoptosis in the pathogenesis of UC may provide a novel strategy for its therapy in clinical practices and the development of new drugs.

Mulberry Anthocyanins Ameliorate DSS-Induced Ulcerative Colitis by Improving Intestinal Barrier Function and Modulating Gut Microbiota

“…Oxidative stress is the underlying mechanism of IBD pathophysiology [ 42 ]. The endogenous self-antioxidant defenses are disrupted with the production of excessive ROS, leading to mucosal rupture and ulceration infiltrated by massive inflammatory cells in the colon tissues [ 43 ]. High concentrations of ROS attack and inactivate endogenous antioxidant factors, such as GSH, SOD, and CAT, thus preventing their effective neutralization of ROS.…”

Inhibiting Ferroptosis: A Novel Approach for Ulcerative Colitis Therapeutics

“…In UC, excessive ROS production by the colorectal mucosa may cause changes in cellular proteins, lipids, and nucleic acids, leading to several cellular dysfunctions that may affect the disease process [ 54 ]. Excess-free iron can aggravate oxidative activity within the intestinal epithelium through multiple mechanisms.…”

Anti-tumor effects of dual PI3K-HDAC inhibitor CUDC-907 on activation of ROS-IRE1α-JNK-mediated cytotoxic autophagy in esophageal cancer

“…Herein we proved this hypothesis and found ROS regulates cancer cell survival [46]. Low concentrations of ROS are involved in cellular signal transduction, whereas excessive ROS can damage proteins and DNA, resulting in autophagy or cell death [46][47][48]. The present results showed that CUDC-907-induced ROS could significantly increase the level of autophagy markers; however, NAC pretreatment could significantly reverse CUDC-907-induced autophagy and cell death, suggesting that CUDC-907 plays an essential role in cell autophagy and death through ROS production.…”

“…The present results showed that CUDC-907-induced ROS could significantly increase the level of autophagy markers; however, NAC pretreatment could significantly reverse CUDC-907-induced autophagy and cell death, suggesting that CUDC-907 plays an essential role in cell autophagy and death through ROS production. Moreover, ROS is one of the secondary messengers and plays a biological role by activating downstream molecules, particularly in the ER stress process [ 47 , 49 , 50 ]. Our experimental results suggested that CUDC-907 promoted autophagic death of esophageal cancer cells through ER stress.…”